Homologous mutations in human ß, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation.

Mutations at a highly conserved homologous residue in three closely related muscle myosins cause three distinct diseases involving muscle defects: R671C in ß-cardiac myosin causes hypertrophic cardiomyopathy, R672C and R672H in embryonic skeletal myosin cause Freeman-Sheldon syndrome, and R674Q in perinatal skeletal myosin causes trismus-pseudocamptodactyly syndrome. It is not known whether their effects at the molecular level are similar to one another or correlate with disease phenotype and severity. To this end, we investigated the effects of the homologous mutations on key factors of molecular power production using recombinantly expressed human ß, embryonic, and perinatal myosin subfragment-1. We found large effects in the developmental myosins but minimal effects in ß myosin, and magnitude of changes correlated partially with clinical severity. The mutations in the developmental myosins dramatically decreased the step size and load-sensitive actin-detachment rate of single molecules measured by optical tweezers, in addition to decreasing overall enzymatic (ATPase) cycle rate. In contrast, the only measured effect of R671C in ß myosin was a larger step size. Our measurements of step size and bound times predicted velocities consistent with those measured in an in vitro motility assay. Finally, molecular dynamics simulations predicted that the arginine to cysteine mutation in embryonic, but not ß, myosin may reduce pre-powerstroke lever arm priming and ADP pocket opening, providing a possible structural mechanism consistent with the experimental observations. This paper presents direct comparisons of homologous mutations in several different myosin isoforms, whose divergent functional effects are a testament to myosin's highly allosteric nature.

Multifactoral immune modulation potentiates durable remission in multiple models of aggressive malignancy.

Tumors typically lack canonical danger signals required to activate adaptive immunity and also frequently employ substantial immunomodulatory mechanisms that downregulate adaptive responses and contribute to escape from immune surveillance. Given the variety of mechanisms involved in shielding tumors from immune recognition, it is not surprising that single-agent immunomodulatory approaches have been largely unsuccessful in generating durable antitumor responses. Here we report a unique combination of immunomodulatory and cytostatic agents that recondition the tumor microenvironment and eliminate complex and/or poor-prognosis tumor types including the non-immunogenic 4T-1 model of TNBC, the aggressive MOC-2 model of HNSCC, and the high-risk MYCN-amplified model of neuroblastoma. A course of therapy optimized for TNBC cured a majority of tumors in both ectopic and orthotopic settings and eliminated metastatic spread in all animals tested at the highest doses. Immune responses were transferable between therapeutic donor and naïve recipient through adoptive transfer, and a sizeable abscopal effect on distant, untreated lesions could be demonstrated experimentally. Similar results were observed in HNSCC and neuroblastoma models, with characteristic remodeling of the tumor microenvironment documented in all model systems. scRNA-seq analysis implicated upregulation of innate immune responses and antigen presentation in tumor cells and the myeloid cell compartment as critical early events. This analysis also highlighted the potential importance of the autonomic nervous system in the governance of inflammatory processes. The data indicate that the targeting of multiple pathways and mechanisms of action can result in substantial synergistic antitumor effects and suggest follow-up in the neoadjuvant setting may be warranted.

Local practice variations and payer differences underlie state-wide disparities in oncoplastic breast surgery.

BACKGROUND: Little is known about disparities in oncoplastic breast surgery delivery. METHODS: The Massachusetts All-Payer Claims Database was queried for patients who received lumpectomy for a diagnosis of breast cancer. Oncoplastic surgery was defined as adjacent tissue transfer, complex trunk repair, reduction mammoplasty, mastopexy, flap-based reconstruction, prosthesis insertion, or unspecified breast reconstruction after lumpectomy. RESULTS: We identified 18 748 patients who underwent lumpectomy between 2016 and 2020. Among those, 3140 patients underwent immediate oncoplastic surgery and 436 patients underwent delayed oncoplastic surgery. Eighty-one percent of patients who underwent oncoplastic surgery did so in the same county as they underwent a lumpectomy. However, the relative frequency of oncoplastic surgery varied significantly among counties. In multivariable regression, public insurance status (odds ratio: 0.87, 95% confidence interval: 0.80-0.95, p = 0.002) was associated with lower odds of undergoing oncoplastic surgery, even after adjusting for macromastia, other comorbidities, and county of lumpectomy. Average payments for lumpectomy with oncoplastic surgery were more than twice as high from private insurers ($840 vs. $1942, p < 0.001). CONCLUSION: Disparities in the receipt of oncoplastic surgery were related to differences in local practice patterns and the type of insurance patients held. Expanding services across counties and considering billing reform may help reduce these disparities.

The efficacy of sleep lifestyle interventions for the management of overweight or obesity in children: a systematic review and meta-analysis.

BACKGROUND: Childhood obesity remains a significant public health concern. Sleep duration and quality among children and youth are suboptimal worldwide. Accumulating evidence suggests an association between inadequate sleep and obesity risk, yet it is unclear whether this relationship is causal. This systematic review examines the efficacy of sleep interventions alone or as a part of lifestyle interventions for the management of overweight or obesity among children and adolescents. METHODS: A keyword/reference search was performed twice, in January 2021 and May 2022 in MEDLINE/PubMed, EMBASE/Ovid, PsycINFO/EBSCO, The Cochrane Library, Web of Science Core Collection/Web of Science, SciELO/Web of Science, and CINAHL/EBSCO. Study eligibility criteria included youth with overweight or obesity between 5 and 17, were RCTs or quasi-randomized, and focused on the treatment of overweight and obesity with a sleep behavior intervention component. Risk of bias was assessed using the Cochrane Risk of Bias assessment tool (RoB2). A Meta-analysis was conducted to estimate the effect of interventions with a sleep component on BMI. The study protocol was registered in PROSPERO (CRD42021233329). RESULTS: A total of 8 studies (2 quasi-experiments, 6 RCTs) met inclusion criteria and accounted for 2,231 participants across 7 countries. Only one study design isolated the effect of sleep in the intervention and reported statistically significant decreases in weight and waist circumference compared to control, though we rated it at high risk of bias. Our meta-analysis showed no significant overall effect on children's BMI as a result of participation in an intervention with a sleep component (Cohen's d = 0.18, 95% CI= -0.04, 0.40, Z = 1.56, P = .11), though caution is warranted due to substantial heterogeneity observed across studies (Tau2 = 0.08; X2 = 23.05, df = 7; I2 = 83.73%). CONCLUSIONS: There were mixed results on the effect of sleep interventions across included studies on BMI, other weight-related outcomes, diet, physical activity, and sleep. Except for one study at low risk of bias, three were rated as 'some concerns' and four 'high risk of bias'. Findings from this study highlight the need for additional RCTs isolating sleep as a component, focusing on children and adolescents living with overweight and obesity.

Geographic Disparities and Payment Variation for Immediate Lymphatic Reconstruction in Massachusetts.

BACKGROUND: Little is known about practice patterns and payments for immediate lymphatic reconstruction (ILR). This study aims to evaluate trends in ILR delivery and billing practices. METHODS: We queried the Massachusetts All-Payer Claims Database between 2016 and 2020 for patients who underwent lumpectomy or mastectomy with axillary lymph node dissection for oncologic indications. We further identified patients who underwent lymphovenous bypass on the same date as tumor resection. We used ZIP code data to analyze the geographic distribution of ILR procedures and calculated physician payments for these procedures, adjusting for inflation. We used multivariable logistic regression to identify variables, which predicted receipt of ILR. RESULTS: In total, 2862 patients underwent axillary lymph node dissection over the study period. Of these, 53 patients underwent ILR. Patients who underwent ILR were younger (55.1 vs 59.3 years, P = 0.023). There were no significant differences in obesity, diabetes, or smoking history between the two groups. A greater percentage of patients who underwent ILR had radiation (83% vs 67%, P = 0.027). In multivariable regression, patients residing in a county neighboring Boston had 3.32-fold higher odds of undergoing ILR (95% confidence interval: 1.76-6.25; P < 0.001), while obesity, radiation therapy, and taxane-based chemotherapy were not significant predictors. Payments for ILR varied widely. CONCLUSIONS: In Massachusetts, patients were more likely to undergo ILR if they resided near Boston. Thus, many patients with the highest known risk for breast cancer-related lymphedema may face barriers accessing ILR. Greater awareness about referring high-risk patients to plastic surgeons is needed.

The Use of Unlisted Billing Codes for Microsurgical Breast Reconstruction and Implications for Code Consolidation.

BACKGROUND: Private insurers have considered consolidating the billing codes presently available for microvascular breast reconstruction. There is a need to understand how these different codes are currently distributed and used to help inform how coding consolidation may impact patients and providers. METHODS: Using the Massachusetts All-Payer Claims Database between 2016 and 2020, patients who underwent microsurgical breast reconstruction following mastectomy for cancer-related indications were identified. Multivariable logistic regression was used to test whether an S2068 claim was associated with insurance type and median household income by patient ZIP code. The ratio of S2068 to CPT19364 claims for privately insured patients was calculated for providers practicing in each county. Total payments for professional fees were compared between billing codes. RESULTS: There were 272 claims for S2068 and 209 claims for CPT19364. An S2068 claim was associated with age < 45 years (OR: 1.89, 95% CI: 1.11-3.20, p = 0.019), more affluent ZIP codes (OR: 1.11, 95% CI: 1.03-1.19, p = 0.004), and private insurance (OR: 16.13, 95% CI: 7.81-33.33, p < 0.001). Median total payments from private insurers were 101% higher for S2068 than for CPT19364. In all but two counties (Worcester and Hampshire), the S-code was used more frequently than CPT19364 for their privately insured patients. CONCLUSION: Coding practices for microsurgical breast reconstruction lacked uniformity in Massachusetts, and payments differed greatly between S2068 and CPT19364. Patients from more affluent towns were more likely to have S-code claims. Coding consolidation could impact access, as the majority of providers in Massachusetts might need to adapt their practices if the S-code were discontinued.

Preoperative Risk Factors for Lymphedema in Inflammatory Breast Cancer.

BACKGROUND: Prophylactic lymphatic bypass or LYMPHA (LYmphatic Microsurgical Preventive Healing Approach) is increasingly offered to prevent lymphedema following breast cancer treatment, which develops in up to 47% of patients. Previous studies focused on intraoperative and postoperative lymphedema risk factors, which are often unknown preoperatively when the decision to perform LYMPHA is made. This study aims to identify preoperative lymphedema risk factors in the high-risk inflammatory breast cancer (IBC) population. METHODS: Retrospective review of our institution's IBC program database was conducted. The primary outcome was self-reported lymphedema development. Multivariable logistic regression analysis was performed to identify preoperative lymphedema risk factors, while controlling for number of lymph nodes removed during axillary lymph node dissection (ALND), number of positive lymph nodes, residual disease on pathology, and need for adjuvant chemotherapy. RESULTS: Of 356 patients with IBC, 134 (mean age: 51 years, range: 22-89 years) had complete data. All 134 patients underwent surgery and radiation. Forty-seven percent of all 356 patients (167/356) developed lymphedema. Obesity (body mass index > 30) (odds ratio [OR]: 2.7, confidence interval [CI]: 1.2-6.4, p = 0.02) and non-white race (OR: 4.5, CI: 1.2-23, p = 0.04) were preoperative lymphedema risk factors. CONCLUSION: Patients with IBC are high risk for developing lymphedema due to the need for ALND, radiation, and neoadjuvant chemotherapy. This study also identified non-white race and obesity as risk factors. Larger prospective studies should evaluate potential racial disparities in lymphedema development. Due to the high prevalence of lymphedema, LYMPHA should be considered for all patients with IBC.

Bridging Heterogeneity Dictates the Microstructure and Yielding Response of Polymer-Linked Emulsions.

Soft materials possessing tunable rheological properties are desirable in applications ranging from 3D printing to biological scaffolds. Here, we use a telechelic, triblock copolymer polystyrene-b-poly(ethylene oxide)-b-polystyrene (SEOS) to form elastic networks of polymer-linked droplets in cyclohexane-in-water emulsions. The SEOS endblocks partition into the dispersed cyclohexane droplets while the midblocks remain in the aqueous continuous phase, resulting in each chain taking on either a looping or bridging conformation. By controlling the fraction of chains that form bridges, we tune the linear elasticity of the emulsions and generate a finite yield stress. Polymers with higher molecular weight (Mw) endblocks form stronger interdroplet connections and display a higher bridging density. Beyond modifying the linear rheology, the telechelic, triblock copolymers also alter the yielding behavior and processability of the linked emulsions. We examine the yield transition of these polymer-linked emulsions through large amplitude oscillatory shear (LAOS) and probe the emulsion structure through confocal microscopy, concluding that polymers that more readily form bridges generate a strongly percolated network, whereas those that are less prone to form bridges tend to produce networks composed of weakly linked clusters of droplets. When yielded, the emulsions consisting of linked clusters break apart into individual clusters that can rearrange upon the application of further shear. By contrast, when the systems containing a more homogeneous bridging density are yielded, the system remains percolated but with reduced elasticity and bridging density. The demonstrated ability of telechelic triblock copolymers to tune not only the linear viscoelasticity of complex fluids but also their nonlinear yield transition enables the use of these polymers as versatile and robust rheological modifiers. We expect our findings to therefore aid the design of the next generation of complex fluids and soft materials.

Toward more rigorous and informative nutritional epidemiology: The rational space between dismissal and defense of the status quo.

To date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rigor and adherence to scientific reporting commensurate with research methods used. Some commentators advocate jettisoning nutritional epidemiology entirely, perhaps believing improvements are impossible. Still others support only normative refinements. But neither abolition nor minor tweaks are appropriate. Nutritional epidemiology, in its present state, offers utility, yet also needs marked, reformational renovation. Changing the status quo will require ongoing, unflinching scrutiny of research questions, practices, and reporting-and a willingness to admit that "good enough" is no longer good enough. As such, a workshop entitled "Toward more rigorous and informative nutritional epidemiology: the rational space between dismissal and defense of the status quo" was held from July 15 to August 14, 2020. This virtual symposium focused on: (1) Stronger Designs, (2) Stronger Measurement, (3) Stronger Analyses, and (4) Stronger Execution and Reporting. Participants from several leading academic institutions explored existing, evolving, and new better practices, tools, and techniques to collaboratively advance specific recommendations for strengthening nutritional epidemiology.

How to make PROMs work: qualitative insights from leaders at United States hospitals with successful PROMs programs.

PURPOSE: Elucidate facilitators, barriers, and key lessons learned regarding the implementation of system-wide clinical patient-reported outcome measure (PROM) programs among United States (US) healthcare leaders. METHODS: We conducted semi-structured interviews with 35 US healthcare leaders, including chief-level executives, data directors, PROM directors, and department chairs involved in PROM implementation across seven diverse healthcare systems from February to June 2020. Transcripts were coded, evaluated for qualitative themes, and categorized according to the consolidated framework for implementation research (CFIR). RESULTS: According to US hospital leaders with experience in existing clinical PROM programs, there are facilitators and barriers to implementation success in each CFIR domain. Allowing clinicians to select PROM measures and ensuring a user-friendly data platform (intervention); adapting data collection to patient home environments (outer setting); informing clinicians of the multi-faceted use of PROM data for research, clinical care, and business (inner setting); implementing PROM education earlier into clinician training (characteristics of individuals); and establishing specialty-agnostic PROM implementation teams (process) were among key facilitators to implementation success. CONCLUSION: Leaders of geographically and clinically diverse PROM programs in the US identify common themes that facilitate successful implementation. Drivers of success depend on factors within and outside the clinical environment. These findings may serve to guide both establishing new PROM programs and refining existing PROM programs.

Disruption of HIV-1 co-receptors CCR5 and CXCR4 in primary human T cells and hematopoietic stem and progenitor cells using base editing.

Disruption of CCR5 or CXCR4, the main human immunodeficiency virus type 1 (HIV-1) co-receptors, has been shown to protect primary human CD4+ T cells from HIV-1 infection. Base editing can install targeted point mutations in cellular genomes, and can thus efficiently inactivate genes by introducing stop codons or eliminating start codons without double-stranded DNA break formation. Here, we applied base editors for individual and simultaneous disruption of both co-receptors in primary human CD4+ T cells. Using cytosine base editors we observed premature stop codon introduction in up to 89% of sequenced CCR5 or CXCR4 alleles. Using adenine base editors we eliminated the start codon in CCR5 in up to 95% of primary human CD4+ T cell and up to 88% of CD34+ hematopoietic stem and progenitor cell target alleles. Genome-wide specificity analysis revealed low numbers of off-target mutations that were introduced by base editing, located predominantly in intergenic or intronic regions. We show that our editing strategies prevent transduction with CCR5-tropic and CXCR4-tropic viral vectors in up to 79% and 88% of human CD4+ T cells, respectively. The engineered T cells maintained functionality and overall our results demonstrate the effectiveness of base-editing strategies for efficient and specific ablation of HIV co-receptors in clinically relevant cell types.

Only one cluster per condition is an invalid design for a cluster randomized trial and should be re-labeled a quasi-experimental study. Response to: "Effect of behavioral activation on time and frequency domain heart rate variability in older adults with subthreshold depression: a cluster randomized controlled trial in Thailand".

Ayudhaya et al. examined the effect of Behavioral Activation on daily step count and heart rate variability among older adults with depression in a study labeled a cluster randomized controlled trial (cRCT). However, only one cluster was assigned to either of the study conditions. Such a design would have zero degrees of freedom for inferential testing, because the variation due to cluster membership cannot be estimated apart from the variation due to treatment assignment. Thus, the intervention effect is completely confounded with the cluster effect. The study should be labeled a quasi-experimental study, not a cRCT. Accordingly, the numerical results should be interpreted as associations but not evidence for causal relationships.

Corrected analysis of "the effects of bright light treatment on affective symptoms in people with dementia: a 24-week cluster randomized controlled trial" that accounts for clustering and nesting verifies conclusions.

In this correspondence, we explain the reasoning for invalidity of the analysis choices by Kolberg et al., and provide the results produced using correct statistical procedures for their study design. Reassuringly, we could verify the original conclusions. That is, results of the corrected statistical models are similar to the results of the original analysis. Regardless of the magnitude of difference that corrected statistical methods make, results and conclusions that are derived from invalid methods are unsubstantiated. By verifying the results, we allow the readers to be assured that the published conclusions in the study by Kolberg et al. now rest on a sound evidential basis.

Is nerve coaptation associated with improved sensation after microvascular breast reconstruction? A systematic review.

BACKGROUND: Sensation after autologous breast reconstruction is an increasingly important outcome. Several studies demonstrated improved sensation with flap neurotization but utilized heterogenous measures and follow-up intervals. This review evaluates sensory outcomes after neurotization using uniform, objective outcome measurements. METHODS: PubMed/Medline and Embase databases were queried for articles published between January 1990 and January 2022. Inclusion criteria included studies with free flap tissue transfer breast reconstruction patients and use of Semmes-Weinstein Monofilaments (SWM) to quantify return of sensation after either neurotization or no neurotization. Reviews, case reports, and studies utilizing implants or pedicled flaps were excluded. RESULTS: Overall, 513 articles were screened. Eleven articles met inclusion criteria for a total of 474 patients. There were 254 non-neurotized patients included as controls (Group A) and 220 neurotized patients (Group B). Mean follow-up time was similar in both groups (22.06 months vs. 22.78 months, p > 0.05). There was no significant difference in age (Group A = 49.97 years vs. Group B = 42.47 years) or BMI (Group A = 25.48 vs. Group B = 25.97) between groups. More patients in group B received radiation therapy (Group B = 32.72% vs. Group A = 20.86%, p > 0.05). Patients that received neurotization had lower mean pressure thresholds (Group A = 38.85 gm/mm2 vs. Group B = 6.69 gm/mm2 , p = 0.053) than comorbidity-matched controls. CONCLUSION: Neurotization has been shown to be a safe and feasible option for enhancing return of sensation after breast reconstruction. Future studies with standardized, long-term follow-up will further elucidate the pattern of breast sensation return and the impact of neurotization.

The Role of Atypical Chemokine Receptors in Neuroinflammation and Neurodegenerative Disorders.

Neuroinflammation is associated with several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Neuroinflammation provides protection in acute situations but results in significant damage to the nervous system if chronic. Overexpression of chemokines within the brain results in the recruitment and activation of glial and peripheral immune cells which can propagate a cascading inflammatory response, resulting in neurodegeneration and the onset of neurodegenerative disorders. Recent work has identified the role of atypical chemokine receptors (ACKRs) in neurodegenerative conditions. ACKRs are seven-transmembrane domain receptors that do not follow canonical G protein signaling, but regulate inflammatory responses by modulating chemokine abundance, location, and availability. This review summarizes what is known about the four ACKRs and three putative ACKRs within the brain, highlighting their known expression and discussing the current understanding of each ACKR in the context of neurodegeneration. The ability of ACKRs to alter levels of chemokines makes them an appealing therapeutic target for neurodegenerative conditions. However, further work is necessary to understand the expression of several ACKRs within the neuroimmune system and the effectiveness of targeted drug therapies in the prevention and treatment of neurodegenerative conditions.

Engineering Human Cells Expressing CRISPR/Cas9-Synergistic Activation Mediators for Recombinant Protein Production.

Recombinant engineering for protein production commonly employs plasmid-based gene templates for introduction and expression of genes in a candidate cell system in vitro. Challenges to this approach include identifying cell types that can facilitate proper post-translational modifications and difficulty expressing large multimeric proteins. We hypothesized that integration of the CRISPR/Cas9-synergistic activator mediator (SAM) system into the human genome would be a powerful tool capable of robust gene expression and protein production. SAMs are comprised of a "dead" Cas9 (dCas9) linked to transcriptional activators viral particle 64 (VP64), nuclear factor-kappa-B p65 subunit (p65), and heat shock factor 1 (HSF1) and are programmable to single or multiple gene targets. We integrated the components of the SAM system into human HEK293, HKB11, SK-HEP1, and HEP-g2 cells using coagulation factor X (FX) and fibrinogen (FBN) as proof of concept. We observed upregulation of mRNA in each cell type with concomitant protein expression. Our findings demonstrate the capability of human cells stably expressing SAM for user-defined singleplex and multiplex gene targeting and highlight their broad potential utility for recombinant engineering as well as transcriptional modulation across networks for basic, translational, and clinical modeling and applications.

How can residents protect and promote pollinators? The diffusion of residential pollinator-friendly gardening.

Urbanization and land use change are leading causes of declines in pollinator abundance and diversity. However, researchers in different regions of the world have found that some pollinators can thrive in urban landscapes, depending on land use practices, environmental conditions, and species traits. Residential landscapes constitute a significant portion of urban green space and thus, residents' adoption of landscape practices to promote pollinators can play a central role in addressing the global pollinator challenge. Yet, although residents' willingness and intention appear strong, adoption of pollinator-friendly gardening remains low. The present study - guided by the Diffusion of Innovations theory - aimed to build empirical understanding by surveying 1598 [State] residents on their experiences and perceptions related to pollinator-friendly gardening to determine the most salient barriers and opportunities to engagement. Key findings suggest making the practice more widely observable and reducing perceived complexity in learning to do the practice are critical to promoting adoption. This demonstrates, in practical terms, that: (1) targeted efforts to build residents' actionable knowledge about pollinator-friendly gardening may significantly reduce uncertainty and boost the likelihood of adoption; and (2) examples of active pollinator gardens need to be more widely showcased and popularized (e.g., through experiential or virtual demonstrations). We also found most residents living in homeowner associations (HOAs) believed HOA policies on pollinator-friendly gardening were restrictive or the residents were unsure whether they are allowed to practice pollinator-friendly gardening. Given these perceptions strongly associated with residents' low intent to engage in pollinator-friendly gardening, a major opportunity exists to diffuse the practice and increase adoption by working with HOAs and community leaders to become promoters of - rather than barriers to - pollinator-friendly gardening.

Misconceptions, Myths, and Mystery: A Cross-sectional Survey Study on Public Knowledge and Values of Microsurgery.

BACKGROUND: Microsurgery is a foundational plastic surgery principle. However, public unawareness of microsurgery and its associated rigorous training in the United States may contribute to current misconceptions and undervaluing of plastic and reconstructive surgeons. This study aims to characterize public knowledge of microsurgery. METHODS: A cross-sectional survey was conducted from August to September 2021 using Amazon Mechanical Turk to assess baseline public knowledge of microsurgery. A multivariable logistic regression model was constructed to evaluate the association between baseline knowledge and demographic characteristics. Significance was set to a p < 0.05. RESULTS: A total of 516 responses were analyzed. The mean age was 36.7 years (standard deviation, 16.04 years; white, 84%; non-Hispanic, 70%). Of those surveyed, 52% agreed that general surgeons perform microsurgery, while only 28% agreed that plastic and reconstructive surgeons perform microsurgery. When asked if head and neck reconstruction, breast reconstruction, and finger replantation required microsurgery, only 28, 41, and 41% of respondents agreed, respectively. When controlled for sociodemographic factors, Hispanics had significantly more odds to mistake that head and neck reconstruction did not require microsurgery (odds ratio [OR] 95% CI 0.49; 0.30-0.80; p = 0.004) and less odds to consider plastic and reconstructive surgeons for reconstruction (OR 0.51; 95% CI 0.32-0.84; p = 0.008). Females had 1.63 more odds of considering plastic and reconstructive surgeons for reconstruction (95% CI 1.09-2.43; p = 0.017). Low-educated participants had significantly more odds to consider general surgeons as those who performed reconstructive microsurgery (OR 8.70; 95% CI 1.09-69.40; p = 0.041). CONCLUSION: Misconceptions of microsurgery as a foundational principle of plastic surgery persist and correlate with undervaluing the specialty. Knowledge differs by ethnicity, level of education, and gender. Therefore, patient counseling should use culturally appropriate elements to demystify microsurgery, build value, and better inform risks and benefits.

Patient-Reported Outcomes and Surgical Quality.

Delivering high-quality surgical care requires knowing how best to define and measure quality in surgery. Patient-reported outcomes (PROs) enable surgeons, health care systems, and payers to understand meaningful health outcomes from the patient's perspective and can be measured using patient-reported outcome measures (PROMs). As a result, there is much interest in using PROMs in routine surgical care, to guide quality improvement and to inform reimbursement pay structures. This chapter defines PROs and PROMs, differentiates PROMs from other quality measures such as patient-reported experience measures, describes PROMs in the context of routine clinical care, and provides an overview of interpreting PROM data. This chapter also describes how PROMs may be applied to quality improvement and value-based reimbursement in surgery.

Design, Synthesis, and Physicochemical Studies of Configurationally Stable ß-Carboline Atropisomers.

Axially chiral atropisomers have energetic barriers to rotation, ΔGrot, that prevent racemization of the respective enantiomers. We used computational modeling to develop a suite of 10 bio-inspired 1-aryl-ß-carbolines with varying ΔGrot, from which a strong structure-activity relationship was observed for 2-substituted-1-naphthyl substituents. We then synthesized two of these atropisomers, 1d and 1f, by a four-step racemic synthesis and resolved the enantiomers via chiral chromatography. Racemization studies revealed experimental ΔGrot values of 39.5 and 33.0 kcal/mol for 1d and 1f, respectively, which were consistent with our computational results. These atropisomers exhibited long half-lives, which allowed for their physicochemical characterization and stereochemical assignment via UV-vis spectroscopy, fluorescence spectroscopy, electronic circular dichroism, and vibrational circular dichroism.