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Time to definitive surgical debridement has been recognized as a predictor for morbidity and mortality in necrotizing soft-tissue infections (NSTI). Rural patients are at particular risk due to limited local resources, decreased access to care, and prolonged transport times. The aim of the current study was to examine the outcomes of NSTI requiring surgical treatment in a previously non-described setting. This retrospective study (2010-2020) from a single tertiary care center in Montana reviewed patients ≥18 years old with a NSTI via ICD9/10 codes. Rural-Urban Continuum Codes (RUCC; characterizing counties by population size) were used to distinguish urban versus rural counties. Race (White and American Indian/Alaskan Native (AI/AN)) was self-described. Qualitative and quantitative comparisons between groups were determined using the appropriate two-tailed statistical tests. An aggregate of 177 patients was identified. Mean age in AI/AN was significantly lower ( P <0.0001) compared to White patients with no preexisting condition delineation. NSTI demonstrated an elevated incidence in both rural areas and AI/AN patients. Diabetes was also significantly higher ( P =0.0073) in rural versus urban patients. Both rural and AI/AN patients faced extended travel distance for treatment. AI/AN patients had a significantly different infection location than White. Furthermore, polymicrobial species were significantly more prevalent in AI/AN patients. Morbidities (defined as septic shock and/or amputation) were significantly higher in AI/AN patients and rural environments ( P <0.01). There was no significant difference in all-cause mortality between respective groups. The state of Montana presents unique challenges to optimizing NSTI treatment due to excessive distances to regional tertiary care facilities. This delay in treatment can lead to increased morbidity., Competing Interests: None., (IJBT Copyright © 2023.)

In this single-center, prospective study we evaluated the impact of an interprofessional education program (IPE) on healthcare students' perceptions of other healthcare professions. The program consisted of four one-hour, roundtable, case-based sessions with students and several facilitators from medicine, nursing, pharmacy, and physician assistant programs. Included students were 18 years of age or older and currently enrolled in a healthcare program during the study time frame. The primary outcome of student perceptions of other healthcare professions was measured by baseline and follow-up surveys using the Adapted Attitudes Toward Interprofessional Health Care Teams scale. Perceptions of students who participated in the IPEP (intervention group) were compared to similar healthcare program students who did not participate in the program (control group). Overall, the intervention group had significantly higher perceptions of other healthcare professions comparing pre-intervention to post -intervention data (pre-intervention mean ± SD of 57.2 ± 5.24; post-intervention mean 60.7 ± 5.63; p = .02). This improvement in perceptions was also seen when comparing the post-intervention group to the control group (control mean 56.7 ± 5.1; post-intervention mean 60.7 ± 5.63; p = .008).

Objectives: The goal of this study was to evaluate a low fixed-dose versus weight-based dosing strategy for four-factor prothrombin complex (4F-PCC) time to administration in intracranial hemorrhage (ICH) patients., Methods: A retrospective analysis was conducted at a single rural Tertiary referral center in patients ≥18 years old on warfarin with ICH who received 4F-PCC. Continuous variables were summarized using mean (±95% CI) and compared using two-tailed tests; p values ≤0.05 were considered statistically significant., Results: A total of 46 ICH patients were reversed using 4F-PCC (Fixed, n = 27 and Weight, n = 19). Baseline characteristics were equivalent. Total units of 4F-PCC (mean dose units 2525.1 versus 1623.3) and dose per kg were significantly reduced in the fixed-dose group. Total time from order to delivery was significantly reduced with the fixed-dose strategy (mean time 43.0 versus 29.0 minutes). Hospital length of stay (LOS), intensive care unit LOS, and mortality were equivalent with a similar mechanism. International Normalized Ratio (INR) reversal success (≤1.5) and total INR change was comparable with no difference in adverse thromboses between groups., Conclusions: A fixed-dosed strategy reduced time to 4F-PCC administration for warfarin reversal in ICH, as compared to a weight-based strategy; with no increase in LOS, mortality, or need for additional dosing. This also resulted in significant cost savings., Competing Interests: None., (IJPPP Copyright © 2023.)

Objectives: The aim of the study was to examine helmet use, incidence of injury, and patient outcomes in a rural cohort of equestrian accidents., Material and Methods: EHR records of patients admitted to a Level II ACS trauma center in the North-west United States were reviewed for helmet use. Injuries were categorized according to International Classification of Diseases-9/10 code., Results: Of 53 identified cases, helmets only reduced superficial injury (χ 2 (1) = 4.837, P = 0.028). Intracranial injury rates were not different between those with and without helmets ( P > 0.05)., Conclusion: In equine related injury, helmets protect against superficial injury but not intracranial injury in Western riders. More investigation is needed to assess why this is the case and determine ways to decrease intracranial injury., Competing Interests: There are no conflicts of interest., (© 2023 Published by Scientific Scholar on behalf of Journal of Neurosciences in Rural Practice.)

Background Nurse residency programs (NRPs) have been proposed to meet the educational needs of new graduate nurses and facilitate the transition into practice. Although most studies indicate the benefits of NRPs to assist nurses during transition into practice, only one study compared an NRP with a control group. This study examined whether nurses in an NRP transitioned into practice more successfully than nurses in a traditional orientation program. Method This study enrolled 106 newly employed graduate nurses into study arms by unit: a nurse residency intervention group or a control group of standard nursing orientation. Casey-Fink Readiness for Practice, Nurse Retention, and Nurse Job Satisfaction surveys measured group outcomes. Results Readiness for practice improved significantly for nurse residents, as did nurse retention perceptions, indicating that nurse residents were more likely to be retained at the organization. The 1- and 2-year nurse retention rates during the 3 years of the study showed marked improvement. Conclusion The NRP resulted in improved readiness for practice, improved nurse retention, and higher job satisfaction compared with standard orientation. [ J Contin Educ Nurs . 2023;54(1):32-39.] .

Background: Black patients are diagnosed with melanoma at a later stage, as compared with their white counterparts. It is unknown if Medicaid expansion might ameliorate this disparity., Methods: Using data from the 2016 National Cancer Database, we conducted a retrospective cohort study. The primary objective was to evaluate whether being diagnosed with melanoma at a Medicaid Expansion State (MES) and black race are associated with a late diagnosis of melanoma.  Main exposure: Being diagnosed in a MES. Secondary exposure: Race. Main outcome: Odds of Stage IV vs Stages 0-III at diagnosis. Univariate, multivariate logistic regression, and propensity score analyses were conducted to evaluate the potential associations. Sub-group analysis was conducted according to age < 65 or ≥ 65 years., Results: A total of 216,604 patients were included, 40-90 years of age, [Formula: see text] 64 years [SD 12.47]. In univariate analysis, patients diagnosed in MES were 15% less likely (95% CI, 0.81-0.88) to be diagnosed with Stage IV melanoma. Black race (vs white) had 3.04 increased odds (95% CI, 2.56-3.60) of late diagnosis. In multivariate analysis, adjusting for socio-economic confounders, patients < 65 years of age were 13% less likely (95% CI, 0.82-0.92) to be diagnosed with Stage IV melanoma. By propensity score analysis, the strength of the associations remained. Black race (vs white) was associated with higher odds (95% CI, 1.91-3.08) of being diagnosed with Stage IV disease. For black patients < 65 years, being diagnosed in a state without Medicaid expansion had 2.55 higher odds (95% CI, 1.93-3.38) of being diagnosed with Stage IV melanoma, which decreased to 2.11 odds (95% CI, 1.34-3.33) in MES. The interaction between race and MES was statistically significant (P = 0.008)., Conclusions: This study suggests that patients are less likely to be diagnosed with Stage IV melanoma in MES. This beneficial effect is more pronounced among Black minorities., (© 2021. W. Montague Cobb-NMA Health Institute.)

This guide describes best practices in using eye tracking technology for research in a variety of disciplines. A basic outline of the anatomy and physiology of the eyes and of eye movements is provided, along with a description of the sorts of research questions eye tracking can address. We then explain how eye tracking technology works and what sorts of data it generates, and provide guidance on how to select and use an eye tracker as well as selecting appropriate eye tracking measures. Challenges to the validity of eye tracking studies are described, along with recommendations for overcoming these challenges. We then outline correct reporting standards for eye tracking studies., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The data presented in this document was created to explore the effect of including or excluding word length, word frequency, the lexical predictability of function words and first pass reading time (or the duration of the first fixation on a word) as either baseline regressors or duration modulators on the final analysis for a fixation-related fMRI investigation of linguistic processing. The effect of these regressors was a central question raised during the review of Linguistic networks associated with lexical, semantic and syntactic predictability in reading: A fixation-related fMRI study [1]. Three datasets were created and compared to the original dataset to determine their effect. The first examines the effect of adding word length and word frequency as baseline regressors. The second examines the effect of removing first pass reading time as a duration modulator. The third examines the inclusion of function word predictability into the baseline hemodynamic response function. Statistical maps were created for each dataset and compared to the primary dataset (published in [1]) across the linguistic conditions of the initial dataset (lexical predictability, semantic predictability or syntax predictability).

The ability to make predictions is thought to facilitate language processing. During language comprehension such predictions appear to occur at multiple levels of linguistic representations (i.e. semantic, syntactic and lexical). The neural mechanisms that define the network sensitive to linguistic predictability have yet to be adequately defined. The purpose of the present study was to explore the neural network underlying predictability during the normal reading of connected text. Predictability values for different linguistic information were obtained from a pre-existing text corpus. Forty-one subjects underwent simultaneous eye-tracking and fMRI scans while reading these select paragraphs. Lexical, semantic, and syntactic predictability measures were then correlated with functional activation associated with fixation onset on the individual words. Activation patterns showed both positive and negative correlations to lexical, semantic, and syntactic predictabilities. Conjunction analysis revealed regions specific to or shared between each type of predictability. The regions associated with the different predictability measures were largely separate. Results suggest that most linguistic predictions are graded in nature, activating components of the existing language system. A number of regions were also found to be uniquely associated with full lexical predictability, most notably the anterior temporal lobe and the inferior posterior temporal cortex., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Eye movements are used to study a variety of cognitive phenomena, including attention, perception, memory, language, reading, decision making, and many others, as well as cognitive impairments and individual differences in cognition. These studies assume, with little evidence, that eye movements are stable across time and trials. Eye movement stability must be better characterized to understand the full theoretical and clinical implications of individual differences in eye movement behavior. The present study examined eye movement reliability in normal individuals during reading. Thirty-nine participants completed 2 sessions of a reading task separated by 1 month. Means and standard deviations of fixation duration, saccade amplitude, first fixation duration, gaze duration, total time, go-past time, skipping, refixation and regression probabilities were compared both between sessions and across trials within sessions. All correlations were highly significant, indicating that eye movement behaviors are stable within individuals across several weeks and highly stable across trials within each individual. The different components of the ex-Gaussian distribution of fixation durations were also highly stable over time. Differences in sensitivity to lexical variables (frequency, predictability, length) were also compared, and were also observed to be highly stable across time. Eye movements in reading are therefore suitable for studying cognition and its neural underpinnings, as well as cognitive development and longitudinal change. Theoretical and clinical implications of these findings are discussed. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Objective: Ex vivo lung perfusion has been successful in the assessment of marginal donor lungs, including donation after cardiac death (DCD) donor lungs. Ex vivo lung perfusion also represents a unique platform for targeted drug delivery. We sought to determine whether ischemia-reperfusion injury would be decreased after transplantation of DCD donor lungs subjected to prolonged cold preservation and treated with an adenosine A2A receptor agonist during ex vivo lung perfusion., Methods: Porcine DCD donor lungs were preserved at 4°C for 12 hours and underwent ex vivo lung perfusion for 4 hours. Left lungs were then transplanted and reperfused for 4 hours. Three groups (n = 4/group) were randomized according to treatment with the adenosine A2A receptor agonist ATL-1223 or the dimethyl sulfoxide vehicle: Infusion of dimethyl sulfoxide during ex vivo lung perfusion and reperfusion (DMSO), infusion of ATL-1223 during ex vivo lung perfusion and dimethyl sulfoxide during reperfusion (ATL-E), and infusion of ATL-1223 during ex vivo lung perfusion and reperfusion (ATL-E/R). Final Pao2/Fio2 ratios (arterial oxygen partial pressure/fraction of inspired oxygen) were determined from samples obtained from the left superior and inferior pulmonary veins., Results: Final Pao2/Fio2 ratios in the ATL-E/R group (430.1 ± 26.4 mm Hg) were similar to final Pao2/Fio2 ratios in the ATL-E group (413.6 ± 18.8 mm Hg), but both treated groups had significantly higher final Pao2/Fio2 ratios compared with the dimethyl sulfoxide group (84.8 ± 17.7 mm Hg). Low oxygenation gradients during ex vivo lung perfusion did not preclude superior oxygenation capacity during reperfusion., Conclusions: After prolonged cold preservation, treatment of DCD donor lungs with an adenosine A2A receptor agonist during ex vivo lung perfusion enabled Pao2/Fio2 ratios greater than 400 mm Hg after transplantation in a preclinical porcine model. Pulmonary function during ex vivo lung perfusion was not predictive of outcomes after transplantation., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Efficient enzymatic hydrolysis of lignocellulosic material remains one of the major bottlenecks to cost-effective conversion of biomass to ethanol. Improvement of glycosylhydrolases, however, is limited by existing medium-throughput screening technologies. Here, we report the first high-throughput selection for cellulase catalysts. This selection was developed by adapting chemical complementation to provide a growth assay for bond cleavage reactions. First, a URA3 counter selection was adapted to link chemical dimerizer activated gene transcription to cell death. Next, the URA3 counter selection was shown to detect cellulase activity based on cleavage of a tetrasaccharide chemical dimerizer substrate and decrease in expression of the toxic URA3 reporter. Finally, the utility of the cellulase selection was assessed by isolating cellulases with improved activity from a cellulase library created by family DNA shuffling. This application provides further evidence that chemical complementation can be readily adapted to detect different enzymatic activities for important chemical transformations for which no natural selection exists. Because of the large number of enzyme variants that selections can now test as compared to existing medium-throughput screens for cellulases, this assay has the potential to impact the discovery of improved cellulases and other glycosylhydrolases for biomass conversion from libraries of cellulases created by mutagenesis or obtained from natural biodiversity.

The widespread use of antibiotics to treat bacterial infections has led to the continuing challenge of antibiotic resistance. For beta-lactam antibiotics, the most common form of resistance is the expression of beta-lactamase enzymes, which inactivate the antibiotics by cleavage of the beta-lactam core. In this study, chemical complementation, which is a general method to link the formation or cleavage of a chemical bond to the transcription of a reporter gene in vivo, was employed in combination with combinatorial mutagenesis to study the mechanism by which the class C beta-lactamase P99 might evolve resistance to the commonly administered third-generation cephalosporin cefotaxime. The chemical complementation system was first shown to be able to distinguish between the wild-type (wt) class C beta-lactamase P99 and the clinically isolated extended-spectrum class C beta-lactamase GC1 in the presence of cefotaxime. The system was then employed to evaluate the activity of mutants of wt P99 towards cefotaxime. A number of single-point mutations at position 221 (Tyr in wt P99) were identified that conferred resistance towards inhibition by cefotaxime, with as much as a 2000-fold increase in k(cat) and a 100-fold increase in k(cat)/K(M) (k(cat)=the rate of catalysis; K(M)=the Michaelis constant), as compared to those of the wt enzyme. Finally, the chemical complementation system was employed in a high-throughput screen to identify a number of mutants of P99 that have multiple mutations around the substrate-binding pocket that increase resistance towards cefotaxime inhibition. The catalytic turnover of cefotaxime by the most active mutant identified was 5500 times higher than that of the wt P99. The resistant mutants suggest a mechanism by which a number of mutations can confer resistance by increasing the flexibility of the Omega loop and altering the positioning of residue 221. Thus, as illustrated in this study, chemical complementation has the potential to be used as a high-throughput screen to study a wide range of enzyme-drug interactions.

The yeast two-hybrid assay has proven to be a powerful method to detect protein-protein interactions as well as to derive genome-wide protein interaction maps. More recently, three-hybrid assays have emerged as a means to detect both protein-RNA and protein-small molecule interactions. Despite the routine use of the two-hybrid assay and the potential of three-hybrid systems, there has been little quantitative characterization to understand how the strength of the protein interaction correlates with transcription activation. It is not known if the additional interaction in three-hybrid systems compromises the sensitivity of the system. Thus, here, we set out to determine the K(D) cutoff of a small molecule three-hybrid system and to determine if there is a correlation between the K(D) and the levels of transcription activation. A series of mutations to FK506-binding protein 12 (FKBP12) were designed to vary the affinity of this protein for the small molecule synthetic ligand for FK506-binding protein 12 (SLF). These FKBP12 variants were overexpressed and purified, and their K(D)'s for SLF were measured using a fluorescence polarization assay. Then the levels of transcription activation in a Mtx-DHFR yeast three-hybrid system were determined for these variants using a lacZ reporter gene. The K(D) cutoff of the Mtx yeast three-hybrid system is found to be ca. 50 nM. Further, the levels of transcription activation correlate with the strength of the binding interaction, though the dynamic range is only 1 order of magnitude. These results establish that the three-hybrid assay has the requisite sensitivity for drug discovery. However, the small dynamic range highlights a limitation to equilibrium-based assays for discriminating interactions based on affinity.

Small-molecule three-hybrid systems show promise as an in vivo alternative to affinity chromatography for detecting small-molecule-protein interactions. While several three-hybrid systems have been reported, little has been done to characterize these systems and, in particular, to test the assumption that the protein-small-molecule interaction can be varied without disrupting the transcription read-out. Recently we reported a dexamethasone-methotrexate chemical inducer of dimerization (CID) for use in the yeast three-hybrid system, based on the well-studied ligand-receptor pairs dexamethasone (Dex)-glucocorticoid receptor (GR) and methotrexate (Mtx)-dihydrofolate reductase (DHFR). Here we describe our first efforts to characterize this system, by focusing on a comparison of the activity of a bacterial and a mammalian DHFR as a test case of the influence of the ligand-receptor pair on the transcription read-out. By using a lacZ reporter gene, the activity of several GR and DHFR protein chimeras with different orientations and linker sequences and Dex-Mtx CIDs with different chemical linkers have been compared. In addition, Western analyses and in vivo biochemical assays have been carried out to confirm the integrity of the GR and DHFR protein chimeras. The transcription read-out is found to be much more sensitive to the structure of the protein chimeras than the CID. The most surprising result is that the levels of transcription activation are consistently higher with the bacterial than the mammalian DHFR, despite the fact that both proteins bind Mtx with an inhibition constant (K(I)) in the low pM range. These results set the stage for understanding three-hybrid systems at the biochemical level so that they can be used to detect ligand-receptor pairs with a range of structures and dissociation constants.

Objectives: To determine the percent volume replacement by an implant and prosthesis, the long-term sequelae of poor volume replacement, and specific guidelines for volume replacement in pediatric patients., Methods: A retrospective observational study of 16 pediatric patients who underwent enucleation (group 1) and 31 adult patients enucleated in childhood (group 2) was performed. The total volume replacement and the volume replacement by the implant were determined. The incidence of secondary surgical procedures for superior sulcus deformity, enophthalmos, ptosis, ectropion, and socket contraction was determined., Results: The average percent volume replaced by the implants in group 1 patients was 68%. The average percent volume replaced by the implants in group 2 patients was 21%. Seventy-one percent of patients in group 2 underwent secondary implant surgery to augment volume and eliminate superior sulcus deformity and enophthalmos., Conclusions: The placement of an adequately sized implant in pediatric patients may obviate the need for secondary augmentation of socket volume in adulthood. The authors suggest an implant 2 mm less in diameter than the axial length of the eye in pediatric patients.

Severe rheumatoid arthritis with rheumatoid nodules on the left upper lid occurred in a 72-year-old woman. Rheumatoid nodules may break down either spontaneously or secondary to trauma. When breakdown occurs, debridement and closure are recommeneded.

A 5-yr-old girl with unilateral retinoblastoma was found to have del(13)(q14.1q14.3). Her 16-month-old sister and 35-year-old mother, with retinal colobomata but without retinoblastoma, have the same deletion. Esterase D studies indicate reduced gene dose at this locus in the 3 females, consistent with a deletion of band 13q14. These patients are of apparently normal intelligence but have a mildly "coarse" facial appearance, a broad nasal bridge, upturned nares, and a long upper lip with thin upper lip vermillion similar to the phenotype suggested by Motegi et al [1983a] for patients with this deletion. Review of the literature documents 2 other patients with deletions of band 13q14 but without retinoblastoma, indicating that retinoblastoma is not a necessary consequence of this deletion. Of the 12 reported patients with deletions limited to band 13q14, seven had normal intelligence and five were macrocephalic. Insufficient clinical information is provided to draw conclusions about phenotype. The family which we describe and those reviewed by Motegi et al suggest that there may be a characteristic appearance in patients with this deletion.