A Neuro-Informatics Pipeline for Cerebrovascular Disease: Research Registry Development.

BACKGROUND: Although stroke is well recognized as a critical disease, treatment options are often limited. Inpatient stroke encounters carry critical information regarding the mechanisms of stroke and patient outcomes; however, these data are typically formatted to support administrative functions instead of research. To support improvements in the care of patients with stroke, a substantive research data platform is needed. OBJECTIVE: To advance a stroke-oriented learning health care system, we sought to establish a comprehensive research repository of stroke data using the Houston Methodist electronic health record (EHR) system. METHODS: Dedicated processes were developed to import EHR data of patients with primary acute ischemic stroke, intracerebral hemorrhage (ICH), transient ischemic attack, and subarachnoid hemorrhage under a review board-approved protocol. Relevant patients were identified from discharge diagnosis codes and assigned registry patient identification numbers. For identified patients, extract, transform, and load processes imported EHR data of primary cerebrovascular disease admissions and available data from any previous or subsequent admissions. Data were loaded into patient-focused SQL objects to enable cross-sectional and longitudinal analyses. Primary data domains (admission details, comorbidities, laboratory data, medications, imaging data, and discharge characteristics) were loaded into separate relational tables unified by patient and encounter identification numbers. Computed tomography, magnetic resonance, and angiography images were retrieved. Imaging data from patients with ICH were assessed for hemorrhage characteristics and cerebral small vessel disease markers. Patient information needed to interface with other local and national databases was retained. Prospective patient outreach was established, with patients contacted via telephone to assess functional outcomes 30, 90, 180, and 365 days after discharge. Dashboards were constructed to provide investigators with data summaries to support access. RESULTS: The Registry of Neurological Endpoint Assessments among Patients with Ischemic and Hemorrhagic Stroke (REINAH) database was constructed as a series of relational category-specific SQL objects. Encounter summaries and dashboards were constructed to draw from these objects, providing visual data summaries for investigators seeking to build studies based on REINAH data. As of June 2022, the database contains 18,061 total patients, including 1809 (10.02%) with ICH, 13,444 (74.43%) with acute ischemic stroke, 1221 (6.76%) with subarachnoid hemorrhage, and 3165 (17.52%) with transient ischemic attack. Depending on the cohort, imaging data from computed tomography are available for 85.83% (1048/1221) to 98.4% (1780/1809) of patients, with magnetic resonance imaging available for 27.85% (340/1221) to 85.54% (11,500/13,444) of patients. Outcome assessment has successfully contacted 56.1% (240/428) of patients after ICH, with 71.3% (171/240) of responders providing consent for assessment. Responders reported a median modified Rankin Scale score of 3 at 90 days after discharge. CONCLUSIONS: A highly curated and clinically focused research platform for stroke data will establish a foundation for future research that may fundamentally improve poststroke patient care and outcomes.

Stroke severity mediates the effect of socioeconomic disadvantage on poor outcomes among patients with intracerebral hemorrhage.

Background: Socioeconomic deprivation drives poor functional outcomes after intracerebral hemorrhage (ICH). Stroke severity and background cerebral small vessel disease (CSVD) burden have each been linked to socioeconomic status and independently contribute to worse outcomes after ICH, providing distinct, plausible pathways for the effects of deprivation. We investigate whether admission stroke severity or cerebral small vessel disease (CSVD) mediates the effect of socioeconomic deprivation on 90-day functional outcomes. Methods: Electronic medical record data, including demographics, treatments, comorbidities, and physiological data, were analyzed. CSVD burden was graded from 0 to 4, with severe CSVD categorized as ≥3. High deprivation was assessed for patients in the top 30% of state-level area deprivation index scores. Severe disability or death was defined as a 90-day modified Rankin Scale score of 4-6. Stroke severity (NIH stroke scale (NIHSS)) was classified as: none (0), minor (1-4), moderate (5-15), moderate-severe (16-20), and severe (21+). Univariate and multivariate associations with severe disability or death were determined, with mediation evaluated through structural equation modelling. Results: A total of 677 patients were included (46.8% female; 43.9% White, 27.0% Black, 20.7% Hispanic, 6.1% Asian, 2.4% Other). In univariable modelling, high deprivation (odds ratio: 1.54; 95% confidence interval: [1.06-2.23]; p = 0.024), severe CSVD (2.14 [1.42-3.21]; p < 0.001), moderate (8.03 [2.76-17.15]; p < 0.001), moderate-severe (32.79 [11.52-93.29]; p < 0.001), and severe stroke (104.19 [37.66-288.12]; p < 0.001) were associated with severe disability or death. In multivariable modelling, severe CSVD (3.42 [1.75-6.69]; p < 0.001) and moderate (5.84 [2.27-15.01], p < 0.001), moderate-severe (27.59 [7.34-103.69], p < 0.001), and severe stroke (36.41 [9.90-133.85]; p < 0.001) independently increased odds of severe disability or death; high deprivation did not. Stroke severity mediated 94.1% of deprivation's effect on severe disability or death (p = 0.005), while CSVD accounted for 4.9% (p = 0.524). Conclusion: CSVD contributed to poor functional outcome independent of socioeconomic deprivation, while stroke severity mediated the effects of deprivation. Improving awareness and trust among disadvantaged communities may reduce admission stroke severity and improve outcomes.

A Contemporary Review of Epidemiology, Risk Factors, Etiology, and Outcomes of Premature Stroke.

PURPOSE OF REVIEW: Recent data identifies increases in young ischemic and hemorrhagic strokes. We provide a contemporary overview of current literature on stroke among young patients or premature stroke along with directions for future investigation. RECENT FINDINGS: Strokes in the young are highly heterogenous and often cryptogenic. Sex distribution and risk factors shift from women among the youngest age groups (< 35) to men over the age of 45, with a coinciding rise in traditional vascular risk factors. Incidence is higher in minority and socioeconomically disadvantaged populations, and the impact of stroke among these communities may be exaggerated by disparities in symptom recognition and access to care. Special diagnostic work-up may be needed, and a lower threshold for diagnosis is warranted as potential misdiagnosis is a concern and may preclude necessary triage and management. Although "premature strokes" form a relatively small proportion of total incidence, they vary greatly across subgroups and present an outsized impact on quality of life and productivity.

Patterned crystal growth and heat wave generation in hydrogels.

The crystallization of metastable liquid phase change materials releases stored energy as latent heat upon nucleation and may therefore provide a triggerable means of activating downstream processes that respond to changes in temperature. In this work, we describe a strategy for controlling the fast, exothermic crystallization of sodium acetate from a metastable aqueous solution into trihydrate crystals within a polyacrylamide hydrogel whose polymerization state has been patterned using photomasks. A comprehensive experimental study of crystal shapes, crystal growth front velocities and evolving thermal profiles showed that rapid growth of long needle-like crystals through unpolymerized solutions produced peak temperatures of up to 45˚C, while slower-crystallizing polymerized solutions produced polycrystalline composites and peaked at 30˚C due to lower rates of heat release relative to dissipation in these regions. This temperature difference in the propagating heat waves, which we describe using a proposed analytical model, enables the use of this strategy to selectively activate thermoresponsive processes in predefined areas.

Spiropyran Photoisomerization Dynamics in Multiresponsive Hydrogels.

Light-responsive, spiropyran-functionalized hydrogels have been used to create reversibly photoactuated structures for applications ranging from microfluidics to nonlinear optics. Tailoring a spiropyran-functionalized hydrogel system for a particular application requires an understanding of how co-monomer composition affects the switching dynamics of the spiropyran chromophore. Such gels are frequently designed to be responsive to different stimuli such as light, temperature, and pH. The coupling of these influences can significantly alter spiropyran behavior in ways not currently well understood. To better understand the influence of responsive co-monomers on the spiropyran isomerization dynamics, we use UV-vis spectroscopy and time-dependent fluorescence intensity measurements to study spiropyran-modified hydrogels polymerized from four common hydrogel precursors of different pH and temperature responsivity: acrylamide, acrylic acid, N-isopropylacrylamide, and 2-(dimethylamino)ethyl methacrylate. In acidic and neutral gels, we observe unusual nonmonotonic, triexponential fluorescence dynamics under 405 nm irradiation that cannot be explicated by either the established spiropyran-merocyanine interconversion model or hydrolysis. To explain these results, we introduce an analytical model of spiropyran interconversions that includes H-aggregated merocyanine and its light-triggered disaggregation under 405 nm irradiation. This model provides an excellent fit to the observed fluorescence dynamics and elucidates exactly how creating an acidic internal gel environment promotes the fast and complete conversion of the hydrophilic merocyanine speciesto the hydrophobic spiropyran form, which is desired in most light-sensitive hydrogel actuators. This can be achieved by incorporating acrylic acid monomers and by minimizing the aggregate concentration. Beyond spiropyran-functionalized gel actuators, these conclusions are particularly critical for nonlinear optical computing applications.

Powering Electronic Devices from Salt Gradients in AA-Battery-Sized Stacks of Hydrogel-Infused Paper.

Strongly electric fish use gradients of ions within their bodies to generate stunning external electrical discharges; the most powerful of these organisms, the Atlantic torpedo ray, can produce pulses of over 1 kW from its electric organs. Despite extensive study of this phenomenon in nature, the development of artificial power generation schemes based on ion gradients for portable, wearable, or implantable human use has remained out of reach. Previously, an artificial electric organ inspired by the electric eel demonstrated that electricity generated from ion gradients within stacked hydrogels can exceed 100 V. The current of this power source, however, was too low to power standard electronics. Here, an artificial electric organ inspired by the unique morphologies of torpedo rays for maximal current output is introduced. This power source uses a hybrid material of hydrogel-infused paper to create, organize, and reconfigure stacks of thin, arbitrarily large gel films in series and in parallel. The resulting increase in electrical power by almost two orders of magnitude compared to the original eel-inspired design makes it possible to power electronic devices and establishes that biology's mechanism of generating significant electrical power can now be realized from benign and soft materials in a portable size.

Fluid surface coatings for solid-state nanopores: comparison of phospholipid bilayers and archaea-inspired lipid monolayers.

In the context of sensing and characterizing single proteins with synthetic nanopores, lipid bilayer coatings provide at least four benefits: first, they minimize unwanted protein adhesion to the pore walls by exposing a zwitterionic, fluid surface. Second, they can slow down protein translocation and rotation by the opportunity to tether proteins with a lipid anchor to the fluid bilayer coating. Third, they provide the possibility to impart analyte specificity by including lipid anchors with a specific receptor or ligand in the coating. Fourth, they offer a method for tuning nanopore diameters by choice of the length of the lipid's acyl chains. The work presented here compares four properties of various lipid compositions with regard to their suitability as nanopore coatings for protein sensing experiments: (1) electrical noise during current recordings through solid-state nanopores before and after lipid coating, (2) long-term stability of the recorded current baseline and, by inference, of the coating, (3) viscosity of the coating as quantified by the lateral diffusion coefficient of lipids in the coating, and (4) the success rate of generating a suitable coating for quantitative nanopore-based resistive pulse recordings. We surveyed lipid coatings prepared from bolaamphiphilic, monolayer-forming lipids inspired by extremophile archaea and compared them to typical bilayer-forming phosphatidylcholine lipids containing various fractions of curvature-inducing lipids or cholesterol. We found that coatings from archaea-inspired lipids provide several advantages compared to conventional phospholipids; the stable, low noise baseline qualities and high viscosity make these membranes especially suitable for analysis that estimates physical protein parameters such as the net charge of proteins as they enable translocation events with sufficiently long duration to time-resolve dwell time distributions completely. The work presented here reveals that the ease or difficulty of coating a nanopore with lipid membranes did not depend significantly on the composition of the lipid mixture, but rather on the geometry and surface chemistry of the nanopore in the solid state substrate. In particular, annealing substrates containing the nanopore increased the success rate of generating stable lipid coatings.

It's Not a Bug, It's a Feature: Functional Materials in Insects.

Over the course of their wildly successful proliferation across the earth, the insects as a taxon have evolved enviable adaptations to their diverse habitats, which include adhesives, locomotor systems, hydrophobic surfaces, and sensors and actuators that transduce mechanical, acoustic, optical, thermal, and chemical signals. Insect-inspired designs currently appear in a range of contexts, including antireflective coatings, optical displays, and computing algorithms. However, as over one million distinct and highly specialized species of insects have colonized nearly all habitable regions on the planet, they still provide a largely untapped pool of unique problem-solving strategies. With the intent of providing materials scientists and engineers with a muse for the next generation of bioinspired materials, here, a selection of some of the most spectacular adaptations that insects have evolved is assembled and organized by function. The insects presented display dazzling optical properties as a result of natural photonic crystals, precise hierarchical patterns that span length scales from nanometers to millimeters, and formidable defense mechanisms that deploy an arsenal of chemical weaponry. Successful mimicry of these adaptations may facilitate technological solutions to as wide a range of problems as they solve in the insects that originated them.

An electric-eel-inspired soft power source from stacked hydrogels.

Progress towards the integration of technology into living organisms requires electrical power sources that are biocompatible, mechanically flexible, and able to harness the chemical energy available inside biological systems. Conventional batteries were not designed with these criteria in mind. The electric organ of the knifefish Electrophorus electricus (commonly known as the electric eel) is, however, an example of an electrical power source that operates within biological constraints while featuring power characteristics that include peak potential differences of 600 volts and currents of 1 ampere. Here we introduce an electric-eel-inspired power concept that uses gradients of ions between miniature polyacrylamide hydrogel compartments bounded by a repeating sequence of cation- and anion-selective hydrogel membranes. The system uses a scalable stacking or folding geometry that generates 110 volts at open circuit or 27 milliwatts per square metre per gel cell upon simultaneous, self-registered mechanical contact activation of thousands of gel compartments in series while circumventing power dissipation before contact. Unlike typical batteries, these systems are soft, flexible, transparent, and potentially biocompatible. These characteristics suggest that artificial electric organs could be used to power next-generation implant materials such as pacemakers, implantable sensors, or prosthetic devices in hybrids of living and non-living systems.

Single channel planar lipid bilayer recordings of the melittin variant MelP5.

MelP5 is a 26 amino acid peptide derived from melittin, the main active constituent of bee venom, with five amino acid replacements. The pore-forming activity of MelP5 in lipid membranes is attracting attention because MelP5 forms larger pores and induces dye leakage through liposome membranes at a lower concentration than melittin. Studies of MelP5 have so far focused on ensemble measurements of membrane leakage and impedance; here we extend this characterization with an electrophysiological comparison between MelP5 and melittin using planar lipid bilayer recordings. These experiments reveal that MelP5 pores in lipid membranes composed of 3:1 phosphatidylcholine:cholesterol consist of an average of 10 to 12 monomers compared to an average of 3 to 9 monomers for melittin. Both peptides form transient pores with dynamically varying conductance values similar to previous findings for melittin, but MelP5 occasionally also forms stable, well-defined pores with single channel conductance values that vary greatly and range from 50 to 3000pS in an electrolyte solution containing 100mM KCl.

Effects of Lipid Tethering in Extremophile-Inspired Membranes on H(+)/OH(-) Flux at Room Temperature.

This work explores the proton/hydroxide permeability (PH+/OH-) of membranes that were made of synthetic extremophile-inspired phospholipids with systematically varied structural elements. A fluorescence-based permeability assay was optimized to determine the effects on the PH+/OH- through liposome membranes with variations in the following lipid attributes: transmembrane tethering, tether length, and the presence of isoprenoid methyl groups on one or both lipid tails. All permeability assays were performed in the presence of a low concentration of valinomycin (10 nM) to prevent buildup of a membrane potential without artificially increasing the measured PH+/OH-. Surprisingly, the presence of a transmembrane tether did not impact PH+/OH- at room temperature. Among tethered lipid monolayers, PH+/OH- increased with increasing tether length if the number of carbons in the untethered acyl tail was constant. Untethered lipids with two isoprenoid methyl tails led to lower PH+/OH- values than lipids with only one or no isoprenoid tails. Molecular dynamics simulations revealed a strong positive correlation between the probability of observing water molecules in the hydrophobic core of these lipid membranes and their proton permeability. We propose that water penetration as revealed by molecular dynamics may provide a general strategy for predicting proton permeability through various lipid membranes without the need for experimentation.

Osmosis-based pressure generation: dynamics and application.

This paper describes osmotically-driven pressure generation in a membrane-bound compartment while taking into account volume expansion, solute dilution, surface area to volume ratio, membrane hydraulic permeability, and changes in osmotic gradient, bulk modulus, and degree of membrane fouling. The emphasis lies on the dynamics of pressure generation; these dynamics have not previously been described in detail. Experimental results are compared to and supported by numerical simulations, which we make accessible as an open source tool. This approach reveals unintuitive results about the quantitative dependence of the speed of pressure generation on the relevant and interdependent parameters that will be encountered in most osmotically-driven pressure generators. For instance, restricting the volume expansion of a compartment allows it to generate its first 5 kPa of pressure seven times faster than without a restraint. In addition, this dynamics study shows that plants are near-ideal osmotic pressure generators, as they are composed of many small compartments with large surface area to volume ratios and strong cell wall reinforcements. Finally, we demonstrate two applications of an osmosis-based pressure generator: actuation of a soft robot and continuous volume delivery over long periods of time. Both applications do not need an external power source but rather take advantage of the energy released upon watering the pressure generators.

An N-heterocyclic carbene/Lewis acid strategy for the stereoselective synthesis of spirooxindole lactones.

A cooperative catalysis approach for the enantioselective formal [3+2] addition of α,ß-unsaturated aldehydes to isatins has been developed. Homoenolate annulations of ß-aryl enals catalyzed by an N-heterocyclic carbene (NHC) require the addition of lithium chloride for high levels of enantioselectivity. This NHC-catalyzed annulation has been used for the total synthesis of maremycin B.

A process for systematically reviewing the literature: providing the research evidence for public health nursing interventions.

BACKGROUND: Several groups have outlined methodologies for systematic literature reviews of the effectiveness of interventions. The Effective Public Health Practice Project (EPHPP) began in 1998. Its mandate is to provide research evidence to guide and support the Ontario Ministry of Health in outlining minimum requirements for public health services in the province. Also, the project is expected to disseminate the results provincially, nationally, and internationally. Most of the reviews are relevant to public health nursing practice. AIMS: This article describes four issues related to the systematic literature reviews of the effectiveness of public health nursing interventions: (1) the process of systematically reviewing the literature, (2) the development of a quality assessment instrument, (3) the results of the EPHPP to date, and (4) some results of the dissemination strategies used. METHODS: The eight steps of the systematic review process including question formulation, searching and retrieving the literature, establishing relevance criteria, assessing studies for relevance, assessing relevant studies for methodological quality, data extraction and synthesis, writing the report, and dissemination are outlined. Also, the development and assessment of content and construct validity and intrarater reliability of the quality assessment questionnaire used in the process are described. RESULTS: More than 20 systematic reviews have been completed. Content validity was ascertained by the use of a number of experts to review the questionnaire during its development. Construct validity was demonstrated through comparisons with another highly rated instrument. Intrarater reliability was established using Cohen's Kappa. Dissemination strategies used appear to be effective in that professionals report being aware of the reviews and using them in program planning/policymaking decisions. CONCLUSIONS: The EPHPP has demonstrated the ability to adapt the most current methods of systematic literature reviews of effectiveness to questions related to public health nursing. Other positive outcomes from the process include the development of a critical mass of public health researchers and practitioners who can actively participate in the process, and the work on dissemination has been successful in attracting external funds. A program of research in this area is being developed.

Tardive dyskinesia--diagnostic issues, subsyndromes, and concurrent movement disorders: a study of state hospital inpatients referred to a movement disorder consultation service.

Of 49 state hospital patients referred for movement disorder consultation for tardive dyskinesia (TD), 11 (23.9%) of 46 meeting inclusion criteria had movement disorders other than TD. These other disorders led to a false diagnosis of TD in 6 subjects (12.2%). Between-day dyskinesia variability affected TD ascertainment in only 3.2 percent of subjects. Prevalences of other neurological conditions in the 30 patients identified with definite TD were parkinsonism (90%), dystonia (25%), akathisia (16%), cerebellar signs (40%), dysmetria (23%), cerebellar tremor (17%), tardive dystonia (3.3%), and tardive akathisia (3.3%). Concurrence rates of parkinsonism with TD varied significantly according to which clinical signs were used to define parkinsonism. Using a rating score threshold of at least mild, rigidity occurred in 79.3 percent, bradykinesia in 55.2 percent, and resting tremor in 41.4 percent of subjects with TD; more significant rigidity occurred in 41.4 percent, bradykinesia in 31.0 percent, and resting tremor in 20.7 percent. Concurrence rates of neurological conditions with TD subsyndromes were distributed rather evenly according to condition prevalences, except for an association of cervicotruncal TD with bradykinesia (perhaps because of ventromedial striatal presynaptic and postsynaptic D2 blockade, respectively). These findings, as well as the occurrence of equal gender ratio and relative under-representation of bipolar and alcohol disorders in subjects with definite TD, are discussed.

Adolescent sexual behaviour: results from an Ontario sample. Part 1: Adolescent sexual activity.

In spite of a variety of broad-based interventions, rates of adolescent sexual intercourse remain high. Using data from a large longitudinal study, this paper provides empirical evidence of Canadian adolescent sexual activity rates by age and gender. The incidence of first sexual intercourse among those 13-15 years was higher among males than females; by ages 16-17 years, rates were the same for both genders (25%). Prevalence of sexual intercourse with age; by age 16-17 years, similar rates were reported for both genders (approximately 50%). Analysis of data over a three-year period indicated that at each age, over 80% of adolescents reported intermittent or no sexual intercourse. Different factors predicted the absence of early sexual intercourse for the two genders. These data provide useful information about Canadian adolescent sexual activity, particularly related to identifying high risk groups for targeted prevention interventions.

Adolescent sexual behaviour: results from an Ontario sample. Part II: Adolescent use of protection.

This paper reports the frequency of use of protection and rates of birth control pill/condom use by age and gender among a large, sexually active group of Ontario adolescents who were followed from 12 to 17 years of age. The sample consisted of the 759 males and 690 females who reported engaging in sexual intercourse during the McMaster Teen Project. Significantly more females aged 15-17 years reported always using a method of protection, and using the birth control pill. Condom use was more frequent among males at all ages, but reached statistical significance at ages 12, 13 and 17 years. Although the numbers reporting no use of protection decreased with age, by 17 years 36% of males and 33% of females continued to report no use of protection. Large numbers of sexually active Ontario adolescents continue to be vulnerable to pregnancy, STDs and AIDS.

Evaluation of an educational program to prevent adolescent pregnancy.

The authors evaluated the effectiveness of a school-based sex education program in decreasing rates of sexual intercourse, improving birth control use, and decreasing the incidence of pregnancies among teenagers 16 years of age and younger. Twenty-one schools received either the McMaster Teen Program or the conventional didactic sex education program. Preprogram, the mean age of the students was 12.6 years. There were no statistically significant differences between groups in time to first sexual activity for males, chi 2(1) = 2.93, p = 0.09; time to first sexual activity for females, chi 2(1) = 0.50, p = 0.48; and time to first pregnancy, chi 2(1) = 1.90, p = 0.17. Significantly more experimental group males reported always using birth control at year 1 (difference 8.9%; 95% confidence interval [CI] = 0.4, 17.4). Limitations of the program that may have influenced the results were the exclusion of contraception information and its short duration.

Childhood sexually transmitted diseases and child sexual abuse: results of a Canadian survey of three professional groups.

The purpose of this national survey was to determine the knowledge and attitudes of Canadian health and social services professionals about the occurrence of sexually transmitted diseases (STDs) in children and its implications for child sexual abuse. A mailed questionnaire was sent to a randomly selected sample of 4,500 nurses, physicians, and youth/social workers across the country. Response rates varied from over 60% of nurses and youth/social workers to only 38% of the physicians. Nurses and youth/social workers were younger than physicians, had a proportionately higher number of females within their groups, and more frequently reported that they had or might have been sexually abused as children. Although there was no statistically significant difference among the groups on the composite knowledge score, physicians scored higher than the other two groups on knowledge about STDs, and youth/social workers had the highest knowledge scores about sexual abuse. Some differences in attitudes among the groups were also noted. Overall, the rates of respondents reporting confidence in their ability to treat children with STDs or child sexual abuse were low (26% and 35% respectively). This paper presents the overall results of the survey, and makes recommendations for strategies to enhance professional expertise in the area.