Stabilization of Synthetic Collagen Triple Helices: Charge Pairs and Covalent Capture.

Collagen mimetic peptides are composed of triple helices. Triple helical formation frequently utilizes charge pair interactions to direct protein assembly. The design of synthetic triple helices is challenging due to the large number of competing species and the overall fragile nature of collagen mimetics. A successfully designed triple helix incorporates both positive and negative criteria to achieve maximum specificity of the supramolecular assembly. Intrahelical charge pair interactions, particularly those involved in lysine-aspartate and lysine-glutamate pairs, have been especially successful both in driving helix specificity and for subsequent stabilization by covalent capture. Despite this progress, the important sequential and geometric relationships of charged residues in a triple helical context have not been fully explored for either supramolecular assembly or covalent capture stabilization. In this study, we compare the eight canonical axial and lateral charge pairs of lysine and arginine with glutamate and aspartate to their noncanonical, reversed charge pairs. These findings are put into the context of collagen triple helical design and synthesis.

Implementing Programs to Initiate Buprenorphine for Opioid Use Disorder Treatment in High-Need, Low-Resource Emergency Departments: A Nonrandomized Controlled Trial.

STUDY OBJECTIVE: We hypothesized that implementation facilitation would enable us to rapidly and effectively implement emergency department (ED)-initiated buprenorphine programs in rural and urban settings with high-need, limited resources and dissimilar staffing structures. METHODS: This multicenter implementation study employed implementation facilitation using a participatory action research approach to develop, introduce, and refine site-specific clinical protocols for ED-initiated buprenorphine and referral in 3 EDs not previously initiating buprenorphine. We assessed feasibility, acceptability, and effectiveness by triangulating mixed-methods formative evaluation data (focus groups/interviews and pre/post surveys involving staff, patients, and stakeholders), patients' medical records, and 30-day outcomes from a purposive sample of 40 buprenorphine-receiving patient-participants who met research eligibility criteria (English-speaking, medically stable, locator information, nonprisoners). We estimated the primary implementation outcome (proportion receiving ED-initiated buprenorphine among candidates) and the main secondary outcome (30-day treatment engagement) using Bayesian methods. RESULTS: Within 3 months of initiating the implementation facilitation activities, each site implemented buprenorphine programs. During the 6-month programmatic evaluation, there were 134 ED-buprenorphine candidates among 2,522 encounters involving opioid use. A total of 52 (41.6%) practitioners initiated buprenorphine administration to 112 (85.1%; 95% confidence interval [CI] 79.7% to 90.4%) unique patients. Among 40 enrolled patient-participants, 49.0% (35.6% to 62.5%) were engaged in addiction treatment 30 days later (confirmed); 26 (68.4%) reported attending one or more treatment visits; there was a 4-fold decrease in self-reported overdose events (odds ratio [OR] 4.03; 95% CI 1.27 to 12.75). The ED clinician readiness increased by a median of 5.02 (95% CI: 3.56 to 6.47) from 1.92/10 to 6.95/10 (n(pre)=80, n(post)=83). CONCLUSIONS: The implementation facilitation enabled us to effectively implement ED-based buprenorphine programs across heterogeneous ED settings rapidly, which was associated with promising implementation and exploratory patient-level outcomes.

Scaling up behavioral science interventions in online education.

Online education is rapidly expanding in response to rising demand for higher and continuing education, but many online students struggle to achieve their educational goals. Several behavioral science interventions have shown promise in raising student persistence and completion rates in a handful of courses, but evidence of their effectiveness across diverse educational contexts is limited. In this study, we test a set of established interventions over 2.5 y, with one-quarter million students, from nearly every country, across 247 online courses offered by Harvard, the Massachusetts Institute of Technology, and Stanford. We hypothesized that the interventions would produce medium-to-large effects as in prior studies, but this is not supported by our results. Instead, using an iterative scientific process of cyclically preregistering new hypotheses in between waves of data collection, we identified individual, contextual, and temporal conditions under which the interventions benefit students. Self-regulation interventions raised student engagement in the first few weeks but not final completion rates. Value-relevance interventions raised completion rates in developing countries to close the global achievement gap, but only in courses with a global gap. We found minimal evidence that state-of-the-art machine learning methods can forecast the occurrence of a global gap or learn effective individualized intervention policies. Scaling behavioral science interventions across various online learning contexts can reduce their average effectiveness by an order-of-magnitude. However, iterative scientific investigations can uncover what works where for whom.

Short-term Satisfaction, Psychosocial Impact, and Complication Profile of Reduction Mammaplasty During Adolescence.

BACKGROUND: Reduction mammaplasty is an effective and safe treatment option for adults with symptomatic macromastia, but there are few data regarding outcomes in adolescents. OBJECTIVES: The purpose of this study was to determine the short-term psychosocial impact, satisfaction, and safety of reduction mammaplasty when performed during adolescence. METHODS: A retrospective review was performed of a single pediatric plastic surgeon's experience with reduction mammaplasty from 2018 to 2021 in patients aged ≤18 years. Patients completed the preoperative and postoperative "Satisfaction with Breasts" and "Psychosocial Well-being" sections of the BREAST-Q survey. Clinical variables gathered included age, weight, BMI, complication profile, specimen resection weight, and follow-up duration. RESULTS: In total, 41 patients met inclusion criteria. The mean converted Rasch scores for BREAST-Q "Satisfaction with Breasts" and "Psychosocial Well-being" increased significantly following reduction mammaplasty ("Satisfaction with Breasts": preoperative, 24.1 vs postoperative, 92.6; "Psychosocial Well-being": preoperative, 37.7 vs postoperative, 90.4; P < .001). Obesity (BMI ≥ 30 kg/m2) was associated with lower preoperative "Psychosocial Well-being" scores (obese, 29.7 vs nonobese, 43.3; P < .001) but a greater improvement in score following surgery (obese, +63.9 vs nonobese, +44.9; P < .001). Specimen weight ≥1000 grams was also associated with greater improvement in score on the "Psychosocial Well-being" section (≥1000 grams, +58 vs <1000 grams, +49.7; P = .046). Overall complication rate was 31.7% while the major complication rate was 2.4%. Mean specimen resection weight was higher in patients who experienced complications (1141.3 grams vs 836.8 grams, P = .008). CONCLUSIONS: Reduction mammaplasty during adolescence predictably improves both short-term satisfaction with breasts and psychosocial well-being while demonstrating a favorable short-term complication profile.

Ratings and experiences in using a mobile application to increase physical activity among university students: implications for future design.

University students have low levels of physical activity and are at risk of mental health disorders. Mobile apps to encourage physical activity can help students, who are frequent smartphone-users, to improve their physical and mental health. Here we report students' qualitative feedback on a physical activity smartphone app with motivational text messaging. We provide recommendations for the design of future apps. 103 students used the app for 6 weeks in the context of a clinical trial (NCT04440553) and answered open-ended questions before the start of the study and at follow-up. A subsample (n = 39) provided additional feedback via text message, and a phone interview (n = 8). Questions focused on the perceived encouragement and support by the app, text messaging content, and recommendations for future applications. We analyzed all transcripts for emerging themes using qualitative coding in Dedoose. The majority of participants were female (69.9%), Asian or Pacific Islander (53.4%), with a mean age of 20.2 years, and 63% had elevated depressive symptoms. 26% felt encouraged or neutral toward the app motivating them to be more physically active. Participants liked messages on physical activity benefits on (mental) health, encouraging them to complete their goal, and feedback on their activity. Participants disliked messages that did not match their motivations for physical activity and their daily context (e.g., time, weekday, stress). Physical activity apps for students should be adapted to their motivations, changing daily context, and mental health issues. Feedback from this sample suggests a key to effectiveness is finding effective ways to personalize digital interventions.

Racial and Ethnic Differences in Presentation and Outcomes for Patients Hospitalized With COVID-19: Findings From the American Heart Association's COVID-19 Cardiovascular Disease Registry.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has exposed longstanding racial and ethnic inequities in health risks and outcomes in the United States. We aimed to identify racial and ethnic differences in presentation and outcomes for patients hospitalized with COVID-19. METHODS: The American Heart Association COVID-19 Cardiovascular Disease Registry is a retrospective observational registry capturing consecutive patients hospitalized with COVID-19. We present data on the first 7868 patients by race/ethnicity treated at 88 hospitals across the United States between January 17, 2020, and July 22, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiovascular events (death, myocardial infarction, stroke, heart failure) and COVID-19 cardiorespiratory ordinal severity score (worst to best: death, cardiac arrest, mechanical ventilation with mechanical circulatory support, mechanical ventilation with vasopressors/inotrope support, mechanical ventilation without hemodynamic support, and hospitalization alone. Multivariable logistic regression analyses were performed to assess the relationship between race/ethnicity and each outcome adjusting for differences in sociodemographic, clinical, and presentation features, and accounting for clustering by hospital. RESULTS: Among 7868 patients hospitalized with COVID-19, 33.0% were Hispanic, 25.5% were non-Hispanic Black, 6.3% were Asian, and 35.2% were non-Hispanic White. Hispanic and Black patients were younger than non-Hispanic White and Asian patients and were more likely to be uninsured. Black patients had the highest prevalence of obesity, hypertension, and diabetes. Black patients also had the highest rates of mechanical ventilation (23.2%) and renal replacement therapy (6.6%) but the lowest rates of remdesivir use (6.1%). Overall mortality was 18.4% with 53% of all deaths occurring in Black and Hispanic patients. The adjusted odds ratios for mortality were 0.93 (95% CI, 0.76-1.14) for Black patients, 0.90 (95% CI, 0.73-1.11) for Hispanic patients, and 1.31 (95% CI, 0.96-1.80) for Asian patients compared with non-Hispanic White patients. The median odds ratio across hospitals was 1.99 (95% CI, 1.74-2.48). Results were similar for major adverse cardiovascular events. Asian patients had the highest COVID-19 cardiorespiratory severity at presentation (adjusted odds ratio, 1.48 [95% CI, 1.16-1.90]). CONCLUSIONS: Although in-hospital mortality and major adverse cardiovascular events did not differ by race/ethnicity after adjustment, Black and Hispanic patients bore a greater burden of mortality and morbidity because of their disproportionate representation among COVID-19 hospitalizations.

Cation-π Interactions and Their Role in Assembling Collagen Triple Helices.

Cation-π interactions play a significant role in the stabilization of globular proteins. However, their role in collagen triple helices is less well understood and they have rarely been used in de novo designed collagen mimetic systems. In this study, we analyze the stabilizing and destabilizing effects in pairwise amino acid interactions between cationic and aromatic residues in both axial and lateral sequential relationships. Thermal unfolding experiments demonstrated that only axial pairs are stabilizing, while the lateral pairs are uniformly destabilizing. Molecular dynamics simulations show that pairs with an axial relationship can achieve a near-ideal interaction distance, but pairs in a lateral relationship do not. Arginine-π systems were found to be more stabilizing than lysine-π and histidine-π. Arginine-π interactions were then studied in more chemically diverse ABC-type heterotrimeric helices, where arginine-tyrosine pairs were found to form the best helix. This work helps elucidate the role of cation-π interactions in triple helices and illustrates their utility in designing collagen mimetic peptides.

Daily Motivational Text Messages to Promote Physical Activity in University Students: Results From a Microrandomized Trial.

BACKGROUND: Low physical activity is an important risk factor for common physical and mental disorders. Physical activity interventions delivered via smartphones can help users maintain and increase physical activity, but outcomes have been mixed. PURPOSE: Here we assessed the effects of sending daily motivational and feedback text messages in a microrandomized clinical trial on changes in physical activity from one day to the next in a student population. METHODS: We included 93 participants who used a physical activity app, "DIAMANTE" for a period of 6 weeks. Every day, their phone pedometer passively tracked participants' steps. They were microrandomized to receive different types of motivational messages, based on a cognitive-behavioral framework, and feedback on their steps. We used generalized estimation equation models to test the effectiveness of feedback and motivational messages on changes in steps from one day to the next. RESULTS: Sending any versus no text message initially resulted in an increase in daily steps (729 steps, p = .012), but this effect decreased over time. A multivariate analysis evaluating each text message category separately showed that the initial positive effect was driven by the motivational messages though the effect was small and trend-wise significant (717 steps; p = .083), but not the feedback messages (-276 steps, p = .4). CONCLUSION: Sending motivational physical activity text messages based on a cognitive-behavioral framework may have a positive effect on increasing steps, but this decreases with time. Further work is needed to examine using personalization and contextualization to improve the efficacy of text-messaging interventions on physical activity outcomes. CLINICALTRIALS.GOV IDENTIFIER: NCT04440553.

Utilization of 3D MRI for the Evaluation of Sphincter Pharyngoplasty Insertion Site in Patients With Velopharyngeal Dysfunction.

Sphincter pharyngoplasty is a surgical method to treat velopharyngeal dysfunction. However, surgical failure is often noted and postoperative assessment frequently reveals low-set pharyngoplasties. Past studies have not quantified pharyngoplasty tissue changes that occur postoperatively and gaps remain related to the patient-specific variables that influence postoperative change. The purpose of this study was to utilize advanced three-dimensional imaging and volumetric magnetic resonance imaging (MRI) data to visualize and quantify pharyngoplasty insertion site and postsurgical tissue changes over time.A prospective, repeated measures design was used for the assessment of craniometric and velopharyngeal variables postsurgically. Imaging was completed across two postoperative time points. Tissue migration, pharyngoplasty dimensions, and predictors of change were analyzed across imaging time points.Significant differences were present between the initial location of pharyngoplasty tissue and the pharyngoplasty location 2 to 4 months postoperatively. The average postoperative inferior movement of pharyngoplasty tissue was 6.82 mm, although notable variability was present across participants. The pharyngoplasty volume decreased by 30%, on average.Inferior migration of the pharyngoplasty tissue was present in all patients. Gravity, scar contracture, and patient-specific variables likely interact, impacting final postoperative pharyngoplasty location. The use of advanced imaging modalities, such as 3D MRI, allows for the quantification and visualization of tissue change. There is a need for continued identification of patient-specific factors that may impact the amount of inferior tissue migration and scar contracture postoperatively.

Holy Simplicity: The Physician's Role in End-of-Life Conversations.

Early initiation of end-of-life (EOL) conversations has been shown to improve patient agency in dying, increase early access to hospice care, and facilitate a dignified death. Despite the benefits of early initiation, EOL conversations do not occur as readily as physicians or patients wish. While medicine is commonly considered both a science and an art, increasing medicalization may narrow a clinician's focus towards procedures or specialized clinical frameworks rather than a patient's end-of-life wishes. Since physicians are ambassadors of clinical knowledge and are trusted patient advocates, it is important they facilitate EOL conversations early in the dying process. Patients desire their physicians to convene these conversations. However, physicians are often hesitant to do so. Notable theologians, philosophers, and physicians offer a broad framework outlining the importance of physician-led EOL conversations.

Treatment and Outcomes of Patients With Ischemic Stroke During COVID-19: An Analysis From Get With The Guidelines-Stroke.

[Figure: see text].

Acute Ischemic Stroke in Patients With COVID-19: An Analysis From Get With The Guidelines-Stroke.

[Figure: see text].

Resource Document for Electroconvulsive Therapy in Adult Correctional Settings.

ABSTRACT: Electroconvulsive therapy (ECT) has been used for decades for the treatment of mental illness. Despite its proven efficacy, ECT is rarely offered to individuals with psychiatric disorders who are incarcerated in jails and prisons. There are currently 2.2 million people confined in US correctional facilities. Research has demonstrated that the prevalence of serious mental illness among the US incarcerated population is 4 to 5 times what is observed in the community, and there can be no doubt that individuals currently exist within jails and prisons who would benefit from this treatment modality. One issue identified as a barrier to ECT being offered to this patient population is a lack of professional guidance on the administration of ECT to individuals who are incarcerated in correctional facilities. Indeed, very little information has been published on this subject in the medical literature. We offer this article as a resource document for the utilization of ECT within adult corrections. This resource document includes a protocol to assist correctional providers and administrators in navigating the ECT referral process, a review of options for delivery of ECT to adult inmate patients, and a discussion of topics related to correctional ECT that warrant special attention, such as informed consent, the perception of ECT use within corrections, ECT-associated cognitive impairment, involuntary ECT, and ECT for competence restoration. It is vital that this important therapy be made accessible to individuals in correctional settings who are experiencing mental illness.

For things to stay the same, things must change: polyploidy and pollen tube growth rates.

BACKGROUND AND AIMS: Pollen tube growth rate (PTGR) is an important single-cell performance trait that may evolve rapidly under haploid selection. Angiosperms have experienced repeated cycles of polyploidy (whole genome duplication), and polyploidy has cell-level phenotypic consequences arising from increased bulk DNA amount and numbers of genes and their interactions. We sought to understand potential effects of polyploidy on several underlying determinants of PTGR - pollen tube dimensions and construction rates - by comparing diploid-polyploid near-relatives in Betula (Betulaceae) and Handroanthus (Bignoniaceae). METHODS: We performed intraspecific, outcrossed hand-pollinations on pairs of flowers. In one flower, PTGR was calculated from the longest pollen tube per time of tube elongation. In the other, styles were embedded in glycol methacrylate, serial-sectioned in transverse orientation, stained and viewed at 1000× to measure tube wall thicknesses (W) and circumferences (C). Volumetric growth rate (VGR) and wall production rate (WPR) were then calculated for each tube by multiplying cross-sectional tube area (πr2) or wall area (W × C), by the mean PTGR of each maternal replicate respectively. KEY RESULTS: In Betula and Handroanthus, the hexaploid species had significantly wider pollen tubes (13 and 25 %, respectively) and significantly higher WPRs (22 and 18 %, respectively) than their diploid congeners. PTGRs were not significantly different in both pairs, even though wider polyploid tubes were predicted to decrease PTGRs by 16 and 20 %, respectively. CONCLUSIONS: The larger tube sizes of polyploids imposed a substantial materials cost on PTGR, but polyploids also exhibited higher VGRs and WPRs, probably reflecting the evolution of increased metabolic activity. Recurrent cycles of polyploidy followed by genome reorganization may have been important for the evolution of fast PTGRs in angiosperms, involving a complex interplay between correlated changes in ploidy level, genome size, cell size and pollen tube energetics.

Accuracy of subjective vesicoureteral reflux timing assessment: supporting new voiding cystourethrogram guidelines.

BACKGROUND: Bladder volume at the onset of vesicoureteral reflux (VUR) is an important prognostic indicator of spontaneous resolution and the risk of pyelonephritis. OBJECTIVE: We aim to determine whether pediatric urologists and pediatric radiologists can accurately estimate the timing of reflux by examining voiding cystourethrogram (VCUG) images without prior knowledge of the instilled contrast volume. MATERIALS AND METHODS: Total bladder volume and the volume at the time of reflux were collected from VCUG reports to determine the volume at the onset of VUR. Thirty-nine patients were sorted into three groups: early-/mid-filling reflux, late-filling and voiding only. Thirty-nine images were shown to three pediatric urologists and two pediatric radiologists in a blinded fashion and they were then asked to estimate VUR timing based on the above categories. A weighted kappa statistic was calculated to assess rater agreement with the gold standard volume-based report of VUR timing. RESULTS: The mean patient age at VCUG was 3.1±2.9 months, the median VUR was grade 3, and 20 patients were female. Overall agreement among all five raters was moderate (k=0.43, 95% confidence interval [CI] 0.36-0.50). Individual agreement between rater and gold standard was slight to moderate with kappa values ranging from 0.13 to 0.43. CONCLUSION: Pediatric radiologists and urologists are unable to accurately and reliably characterize VUR timing on fluoroscopic VCUG. These findings support the recently published American Academy of Pediatrics protocol recommending the routine recording of bladder volume at the onset of VUR as a standard component of all VCUGs to assist in a more accurate assessment of the likelihood of resolution and risk of recurrent urinary tract infections.

Nonprofessional Peer Support to Improve Mental Health: Randomized Trial of a Scalable Web-Based Peer Counseling Course.

BACKGROUND: Millions of people worldwide are underserved by the mental health care system. Indeed, most mental health problems go untreated, often because of resource constraints (eg, limited provider availability and cost) or lack of interest or faith in professional help. Furthermore, subclinical symptoms and chronic stress in the absence of a mental illness diagnosis often go unaddressed, despite their substantial health impact. Innovative and scalable treatment delivery methods are needed to supplement traditional therapies to fill these gaps in the mental health care system. OBJECTIVE: This study aims to investigate whether a self-guided web-based course can teach pairs of nonprofessional peers to deliver psychological support to each other. METHODS: In this experimental study, a community sample of 30 dyads (60 participants, mostly friends), many of whom presented with mild to moderate psychological distress, were recruited to complete a web-based counseling skills course. Dyads were randomized to either immediate or delayed access to training. Before and after training, dyads were recorded taking turns discussing stressors. Participants' skills in the helper role were assessed before and after taking the course: the first author and a team of trained research assistants coded recordings for the presence of specific counseling behaviors. When in the client role, participants rated the session on helpfulness in resolving their stressors and supportiveness of their peers. We hypothesized that participants would increase the use of skills taught by the course and decrease the use of skills discouraged by the course, would increase their overall adherence to the guidelines taught in the course, and would perceive posttraining counseling sessions as more helpful and their peers as more supportive. RESULTS: The course had large effects on most helper-role speech behaviors: helpers decreased total speaking time, used more restatements, made fewer efforts to influence the speaker, and decreased self-focused and off-topic utterances (ds=0.8-1.6). When rating the portion of the session in which they served as clients, participants indicated that they made more progress in addressing their stressors during posttraining counseling sessions compared with pretraining sessions (d=1.1), but they did not report substantive changes in feelings of closeness and supportiveness of their peers (d=0.3). CONCLUSIONS: The results provide proof of concept that nonprofessionals can learn basic counseling skills from a scalable web-based course. The course serves as a promising model for the development of web-based counseling skills training, which could provide accessible mental health support to some of those underserved by traditional psychotherapy.

Effects of Phase Polarity and Charge Balance Spinal Cord Stimulation on Behavior and Gene Expression in a Rat Model of Neuropathic Pain.

OBJECTIVE: To investigate the effect of phase polarity and charge balance of spinal cord stimulation (SCS) waveforms on pain behavior and gene expression in a neuropathic pain rodent model. We hypothesized that differing waveforms will result in diverse behavioral and transcriptomics expression due to unique mechanisms of action. MATERIALS AND METHODS: Rats were implanted with a four-contact cylindrical mini-lead and randomly assigned to two control (no-pain and pain model) and five test groups featuring monophasic, as well as charge-unbalanced and charge-balanced biphasic SCS waveforms. Mechanical and cold allodynia were assessed to measure efficacy. The ipsilateral dorsal quadrant of spinal cord adjacent to the lead was harvested post-stimulation and processed to determine gene expression via real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Gene expression, SCS intensity (mA), and behavioral score as percent of baseline (BSPB) were statistically analyzed and used to generate correlograms using R-Studio. Statistical analysis was performed using SPSS22.0, and p < 0.05 was considered significant. RESULTS: As expected, BSPB was significantly lower for the pain model group compared to the no-pain group. BSPB was significantly improved post-stim compared to pre-stim using cathodic, anodic, symmetric biphasic, or asymmetric biphasic 1:2 waveforms; however, BSPB was not restored to Sham levels. RT-PCR analysis showed that eight genes demonstrated a significant difference between the pain model and SCS waveforms and between waveforms. Correlograms reveal a linear correlation between regulation of expression of a given gene in relation to mA, BSPB, or other genes. CONCLUSIONS: Our results exhibit that specific SCS waveforms differentially modulate several key transcriptional pathways that are relevant in chronic pain conditions. These results have significant implications for SCS: whether to move beyond traditional paradigm of neuronal activation to focus also on modulating immune-driven processes.

Expanded Analysis of a Modified Enhanced Recovery Protocol in Cleft Palatoplasty.

OBJECTIVE: We have previously shown the efficacy of an enhanced recovery after surgery (ERAS) protocol in pediatric cleft palatoplasty for proof of concept (POC). We sought to validate the efficacy of ERAS when expanded to patients of variable age and complexity undergoing primary palatoplasty. MAIN OUTCOME MEASURE(S): Between April 2017 and December 2018, 100 patients were collected prospectively for the expanded assessment (ERAS2) and POC (ERAS1) and compared to historical controls both independently and in aggregate (ERAS(T)). We compared patient demographics, perioperative narcotic administration, length of stay (LOS), and rates of return to service (RTS). RESULTS: Despite increased complexity, total narcotic usage (morphine equivalents normalized per weight) during each phase of care was significantly greater in controls when compared to ERAS1, ERAS2, or ERAST, respectively (intraoperative: 0.44 mg/kg vs 0.013 mg/kg vs 0.016 mg/kg vs 0.014 mg/kg; postanesthesia care unit: 0.061 mg/kg vs 0.006 mg/kg vs 0.007 mg/kg vs 0.007 mg/kg; postoperative: 0.389 mg/kg vs 0.009 mg/kg vs 0.026 mg/kg vs 0.017 mg/kg). ERAS1 and ERAS2 groups each demonstrated a decrease in LOS (-36.6%, -26.3%) when compared to controls. Overall, application of ERAS led to a 95.7% reduction in narcotic administration and a 31.7% decrease in LOS when compared to controls. The incidence of RTS was higher in ERAS2 (13.0%) when compared to ERAS1 (2.1%) or controls (2.4%), with the strongest independent predictor being a positive perioperative respiratory viral panel (PRVP). CONCLUSIONS: Application of ERAS to palatoplasty patients of advanced age and complexity evidenced consistency with respect to decreased perioperative narcotic administration and shortened LOS. A positive PRVP was found to be an independent predictor of RTS even when ERAS was applied.

Lipid Bilayer Thickness Measured by Quantitative DIC Reveals Phase Transitions and Effects of Substrate Hydrophilicity.

Quantitative differential interference contrast microscopy is demonstrated here as a label-free method, which is able to image and measure the thickness of lipid bilayers with 0.1 nm precision. We investigate the influence of the substrate on the thickness of fluid-phase 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)-supported lipid bilayers and find a thinning of up to 10%, depending on substrate hydrophilicity, local bilayer coverage, and ionic strength of the medium. With fluorescently labeled lipid bilayers, we also observe changes in the bilayer thickness depending on the choice of fluorophore. Furthermore, liquid-ordered domains in bilayers, formed from DOPC, cholesterol, and sphingomyelin, are measured, and the corresponding thickness change between the liquid-ordered and liquid-disordered phases is accurately determined. Again, the thickness difference is found to be dependent on the presence of the fluorophore label, highlighting the need for quantitative label-free techniques.

How does genome size affect the evolution of pollen tube growth rate, a haploid performance trait?

PREMISE: Male gametophytes of most seed plants deliver sperm to eggs via a pollen tube. Pollen tube growth rates (PTGRs) of angiosperms are exceptionally rapid, a pattern attributed to more effective haploid selection under stronger pollen competition. Paradoxically, whole genome duplication (WGD) has been common in angiosperms but rare in gymnosperms. Pollen tube polyploidy should initially accelerate PTGR because increased heterozygosity and gene dosage should increase metabolic rates. However, polyploidy should also independently increase tube cell size, causing more work which should decelerate growth. We asked how genome size changes have affected the evolution of seed plant PTGRs. METHODS: We assembled a phylogenetic tree of 451 species with known PTGRs. We then used comparative phylogenetic methods to detect effects of neo-polyploidy (within-genus origins), DNA content, and WGD history on PTGR, and correlated evolution of PTGR and DNA content. RESULTS: Gymnosperms had significantly higher DNA content and slower PTGR optima than angiosperms, and their PTGR and DNA content were negatively correlated. For angiosperms, 89% of model weight favored Ornstein-Uhlenbeck models with a faster PTGR optimum for neo-polyploids, whereas PTGR and DNA content were not correlated. For within-genus and intraspecific-cytotype pairs, PTGRs of neo-polyploids < paleo-polyploids. CONCLUSIONS: Genome size increases should negatively affect PTGR when genetic consequences of WGDs are minimized, as found in intra-specific autopolyploids (low heterosis) and gymnosperms (few WGDs). But in angiosperms, the higher PTGR optimum of neo-polyploids and non-negative PTGR-DNA content correlation suggest that recurrent WGDs have caused substantial PTGR evolution in a non-haploid state.