To compare visual outcomes between wavefront-guided photorefractive keratectomy (PRK) and wavefront-guided laser in situ keratomileusis (LASIK).
Academic center, Salt Lake City, Utah, USA.
In this ...randomized prospective study, myopic eyes were treated with wavefront-guided PRK and or wavefront-guided LASIK using a Visx Star S4 CustomVue platform with iris registration. Primary outcome measures were uncorrected (UDVA) and corrected (CDVA) distance visual acuities and manifest refraction. Secondary outcome measures were higher-order aberrations (HOAs) and contrast sensitivity.
The PRK group comprised 101 eyes and the LASIK group, 102 eyes. At 6 months, the mean UDVA was -0.03 logMAR +/- 0.10 SD (20/19) and 0.07 +/- 0.09 logMAR (20/24), respectively (P = .544). In both groups, 75% eyes achieved a UDVA of 20/20 or better (P = .923); 77% of eyes in the PRK group and 88% in the LASIK group were within +/-0.50 diopter of emmetropia (P = .760). There was no statistically significant difference between groups in contrast sensitivity at 3, 6, 12, or 18 cycles per degree. The mean postoperative HOA root mean square was 0.45 +/- 0.13 mum in the PRK group and 0.59 +/- 0.22 mum in the LASIK group (P = .012), representing an increase factor of 1.22 and 1.74, respectively.
Wavefront-guided PRK and wavefront-guided LASIK had similar efficacy, predictability, safety, and contrast sensitivity; however, wavefront-guided PRK induced statistically fewer HOAs than wavefront-guided LASIK at 6 months.
No author has a financial or proprietary interest in any material or method mentioned.
Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as promising drug delivery vehicles for small RNAs (siRNA and miRNA) due to their natural role in intercellular RNA ...transport. However, the application of EVs for therapeutic RNA delivery may be limited by loading approaches that can induce cargo aggregation or degradation. Here, we report the use of sonication as a means to actively load functional small RNAs into EVs. Conditions under which EVs could be loaded with small RNAs with minimal detectable aggregation were identified, and EVs loaded with therapeutic siRNA
via
sonication were observed to be taken up by recipient cells and capable of target mRNA knockdown leading to reduced protein expression. This system was ultimately applied to reduce expression of HER2, an oncogenic receptor tyrosine kinase that critically mediates breast cancer development and progression, and could be extended to other therapeutic targets. These results define important parameters informing the application of sonication as a small RNA loading method for EVs and demonstrate the potential utility of this approach for versatile cancer therapy.
Microfluidic lumen-based systems are microscale models that recapitulate the anatomy and physiology of tubular organs. These technologies can mimic human pathophysiology and predict drug response, ...having profound implications for drug discovery and development. Herein, we review progress in the development of microfluidic lumen-based models from the 2000s to the present. The core of the review discusses models for mimicking blood vessels, the respiratory tract, the gastrointestinal tract, renal tubules, and liver sinusoids, and their application to modeling organ-specific diseases. We also highlight emerging application areas, such as the lymphatic system, and close the review discussing potential future directions.
Microfluidic lumen-based systems are microscale models that recapitulate the anatomy and physiology of tubular organs. Here, we review recent microfluidic lumen-based systems and their applications in basic and translational biomedical research.
The authors report a series of studies designed to
determine whether effects similar to those observed in the innate
categorical perception of color and phonemes are induced during the
learning of ...simple unidimensional categories and more complex
multidimensional ones. In Experiment 1 no evidence was found for
such effects when stimuli varied on 1 dimension. Experiments 2 and 3
demonstrated a within-category compression effect but no
between-category expansion effect for stimuli varying in 2
dimensions. Compression only was also shown in Experiment 4, which
used pictures of actual objects. Multidimensional scaling analyses
illustrate how within-category compression without expansion was
sufficient to produce categorical clustering of items in the
similarity space. These analyses also show that learning changed the
dimensional structure of similarity space. Results are compared with
those from other studies exploring similar phenomena and with neural
network simulations.
Cyclic electron flow (CEFI) has been proposed to balance the chloroplast energy budget, but the pathway, mechanism, and physiological role remain unclear. We isolated a new class of mutant in ...Arabidopsis thaliana, hcef for high CEF1, which shows constitutively elevated CEF1. The first of these, hcef1, was mapped to chloroplast fructose-1,6-bisphosphatase. Crossing hcef1 with pgr5, which is deficient in the antimycin A-sensitive pathway for plastoquinone reduction, resulted in a double mutant that maintained the high CEF1 phenotype, implying that the PGR5-dependent pathway is not involved. By contrast, crossing hcef1 with crr2-2, deficient in thylakoid NADPH dehydrogenase (NDH) complex, results in a double mutant that is highly light sensitive and lacks elevated CEF1, suggesting that NDH plays a direct role in catalyzing or regulating CEF1. Additionally, the NdhI component of the NDH complex was highly expressed in hcef1, whereas other photosynthetic complexes, as well as PGR5, decreased. We propose that (1) NDH is specifically upregulated in hcef1, allowing for increased CEF1; (2) the hcef1 mutation imposes an elevated ATP demand that may trigger CEF1; and (3) alternative mechanisms for augmenting ATP cannot compensate for the loss of CEF1 through NDH.
To provide a descriptive analysis of scrotal and testicular trauma in the USA. Additionally, we hypothesized that motorcycle collision would have a higher association with scrotal or testicular ...trauma and subsequent scrotal or testicular operation, compared to a bicycle collision.
The National Trauma Data Bank (2007-2015) was queried to identify adult male patients with scrotal or testicular trauma. A multivariable logistic regression analysis was performed.
A total of 8,030 patients (0.23%) had scrotal/testicular injury, with 44.6% involved in blunt trauma. A penetrating mechanism occurred in 50.5% of cases, with assault by firearm (75.8%) being the most common. The median age of the patients was 31 years and the median injury severity score was 8. Most had isolated scrotal or testicular trauma (74.5%), with 48.3% requiring scrotal or testicular operation, most commonly repair of laceration (37.3%). Patients involved in a motorcycle collision had higher risk for scrotal/testicular trauma (OR=5.40, CI=4.40-6.61,
=0.0004) and subsequent scrotal/testicular surgery (OR=4.93, CI=3.82-6.36,
=0.0005), compared to bicycle collision.
Scrotal or testicular trauma is rare but occurs most commonly after assault by firearm. Most patients only have isolated scrotal or testicular trauma, but nearly half require subsequent scrotal or testicular operation. Trauma patients presenting after a motorcycle collision have a higher association of scrotal or testicular trauma and subsequent surgery when compared to those involved in a bicycle collision.
To determine whether supplementing retinyl palmitate (RP) to vitamin A-deficient or -adequate chicks during vaccination increased the antibody response, an experiment was conducted that used a ...2-generational model. White Leghorn chicks were hatched from eggs that contained 1.06 ± 0.13, 1.41 ± 0.14, or 1.90 ± 0.13 μg of retinol/g of egg yolk. Upon hatch, chicks were allotted to a diet that contained 70, 100, or 130% of the vitamin A requirement (1,500 IU/kg). At 14 d of age, chicks were challenged with keyhole limpet hemocyanin (KLH), Freund's incomplete adjuvant (FIA), KLH and FIA, KLH and RP administered in the same injection, or KLH and RP administered at different injection sites. The RP dosage was 7,000 IU/kg of BW, and dosage of the KLH was 1 mg/kg of BW. Chicks were bled and rechallenged at 19 d of age, and a final blood draw was taken at 29 d of age. The IgM and IgG antibody responses to KLH were determined by ELISA, and agglutination was used to determine natural antibody titers. When compared with chicks fed diets that contained 70 and 100% of the vitamin A requirement, the chicks fed 130% of the vitamin A requirement had a lower primary IgM and IgG antibody response (P < 0.02) and the secondary IgG response was significantly lower (P = 0.004). However, administering RP together or separate from KLH did not significantly change the secondary IgM or IgG responses compared with chicks challenged with KLH and FIA (P < 0.01). Moreover, natural antibody titers were not different among dietary treatments (P = 0.91). In conclusion, administration of RP with KLH did not improve antibody response in chicks.
BACKGROUND: The Centers for Disease Control and Prevention (CDC) Guideline for Hand Hygiene in Health Care Settings was issued in 2002. In 2003, the Joint Commission on Accreditation of Healthcare ...Organizations (JCAHO) established complying with the CDC Guideline as a National Patient Safety Goal for 2004. This goal has been maintained through 2006. The CDC's emphasis on the use of alcohol‐based hand rubs (ABHRs) rather than soap and water was an opportunity to improve compliance, but the Guideline contained over 40 specific recommendations to implement.
OBJECTIVE: To use the Six Sigma process to examine hand hygiene practices and increase compliance with the CDC hand hygiene recommendations required by JCAHO.
DESIGN: Six Sigma Project with pre‐post design.
PARTICIPANTS: Physicians, nurses, and other staff working in 4 intensive care units at 3 hospitals.
MEASUREMENTS: Observed compliance with 10 required hand hygiene practices, mass of ABHR used per month per 100 patient‐days, and staff attitudes and perceptions regarding hand hygiene reported by questionnaire.
RESULTS: Observed compliance increased from 47% to 80%, based on over 4,000 total observations. The mass of ABHR used per 100 patient‐days in 3 intensive care units (ICUs) increased by 97%, 94%, and 70%; increases were sustained for 9 months. Self‐reported compliance using the questionnaire did not change. Staff reported increased use of ABHR and increased satisfaction with hand hygiene practices and products.
CONCLUSIONS: The Six Sigma process was effective for organizing the knowledge, opinions, and actions of a group of professionals to implement the CDC's evidence‐based hand hygiene practices in 4 ICUs. Several tools were developed for widespread use.
Trauma patients with burn injuries have higher morbidity and mortality rates compared with patients who solely experience burn or trauma injuries. There is a paucity of data regarding burn-trauma ...(BT) patient outcomes at level I (LI) trauma centers compared with level II (LII) centers. We hypothesized that BT patients at LI trauma centers have lower mortality rates than those at LII trauma centers.
The Trauma Quality Improvement Program (2010-2016) was queried for patients aged ≥18 y who had BT injuries. Patients treated at an LI were compared with those at an LII center with a primary outcome of in-hospital mortality. Secondary outcomes included hospital length of stay (LOS) and intensive care unit (ICU) LOS. A multivariable logistic regression analysis was used to identify factors associated with all-cause mortality.
From 1971 BT patients, 1540 (78%) were treated at an LI trauma center, and 431 (22%) at an LII center. Compared with LII centers, LI BT patients had a longer median LOS (10 versus 7 d; P < 0.001) and ICU LOS (5 versus 4 d; P < 0.001). Both LI and LII centers had similar mortality rates (8.5% versus 7.0%; P = 0.300). On multivariable analysis, receiving care at an LI trauma center was not associated with decreased mortality (odds ratio 0.79, 95% confidence interval 0.42-1.48; P = 0.456).
We report that LI trauma center BT patients had an increased hospital and ICU LOS compared with those at LII centers. However, there was no significant difference in mortality between patients cared for at LI and LII trauma centers in risk-adjusted models.
Artificial antigen presenting cells are biomimetic particles that recapitulate the signals presented by natural antigen presenting cells in order to stimulate T cells in an antigen-specific manner ...using an acellular platform. We have engineered an enhanced nanoscale biodegradable artificial antigen presenting cell by modulating particle shape to achieve a nanoparticle geometry that allows for increased radius of curvature and surface area for T cell contact. The non-spherical nanoparticle artificial antigen presenting cells developed here have reduced nonspecific uptake and improved circulation time compared both to spherical nanoparticles and to traditional microparticle technologies. Additionally, the anisotropic nanoparticle artificial antigen presenting cells efficiently engage with and activate T cells, ultimately leading to a marked anti-tumor effect in a mouse melanoma model that their spherical counterparts were unable to achieve.
Artificial antigen presenting cells (aAPC) can activate antigen-specific CD8+ T cells but have largely been limited to microparticle-based platforms and ex vivo T cell expansion. Although more amenable to in vivo use, nanoscale aAPC have traditionally been ineffective due to limited surface area available for T cell interaction. In this work, we engineered non-spherical biodegradable nanoscale aAPC to investigate the role of particle geometry and develop a translatable platform for T cell activation. The non-spherical aAPC developed here have increased surface area and a flatter surface for T cell engagement and, therefore, can more effectively stimulate antigen-specific T cells, resulting in anti-tumor efficacy in a mouse melanoma model.
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