Foundational features of indigenous pregnancy care: Lessons learned from indigenous pregnancy care providers.

PROBLEM: Indigenous populations experience higher odds of poor maternal and infant health outcomes than non-Hispanic White mothers yet have lower odds of receiving adequate prenatal care. BACKGROUND: Many Indigenous communities rely on modern Western medical institutions to provide pregnancy related health care. These systems were not developed with or for Indigenous communities and often fail to meet the needs of Indigenous pregnant patients. Offering culturally congruent models of care may increase prenatal care utilization. QUESTION, HYPOTHESIS OR AIM: This paper used qualitative inquiry to identify Indigenous approaches to caring for pregnancy. METHODS: Our team conducted 16 semi-structured individual interviews and one group interview with a total of 19 respondents. To arrive at thematic categories, the research team engaged in a modified pile sorting technique. The final set of categories, along with sub-themes, descriptions and example quotes, were sent to interviewees for approval. FINDINGS: Ten Foundational Features of Indigenous Pregnancy Care were identified. These covered themes related to Indigenous cultural practices, relationships, Indigenous sovereignty, local Indigenous community, full spectrum care, wholistic care, birthing person's wisdom, power and autonomy, flexibility, historical trauma, and cultural awareness. DISCUSSION: Modern midwifery care delivered by Indigenous practitioners may partially bridge the cultural gap; however, intentional effort is needed to integrate Indigenous ways into medical doctor practice models and facilities. CONCLUSION: This paper identifies ten foundational features of Indigenous pregnancy care and demonstrates the importance of recognizing the effects of trauma and providing opportunities for healing, upholding sovereignty, and centering relationships when caring for Indigenous pregnancies.

Barriers and Facilitators of Surrogates Providing Consent for Critically Ill Patients in Clinical Trials: A Qualitative Study.

BACKGROUND: Enrollment into critical care clinical trials is often hampered by the need to rely on surrogate decision-makers. To identify potential interventions facilitating enrollment into critical care clinical trials, a better understanding of surrogate decision-making for critical care clinical trial enrollment is needed. RESEARCH QUESTION: What are the barriers and facilitators of critical care trial enrollment? What are surrogate decision-makers' perspectives on proposed interventions to facilitate trial enrollment? STUDY DESIGN AND METHODS: We conducted semistructured interviews with 20 surrogate decision-makers of critically ill patients receiving mechanical ventilation. The interviews were recorded and transcribed verbatim, and analyzed for themes using an inductive approach. RESULTS: Thematic analysis confirmed previous research showing that trust in the system, assessing the risks and benefits of trial participation, the desire to help others, and building medical knowledge as important motivating factors for trial enrollment. Two previously undescribed concerns among surrogate decision-makers of critically ill patients were identified, including the potential to interfere with clinical treatment decisions and negative sentiment about placebos. Surrogates viewed public recognition and charitable donations for participation as favorable potential interventions to encourage trial enrollment. However, participants viewed direct financial incentives and prioritizing research participants during medical rounds negatively. INTERPRETATION: This study confirms and extends previous findings that health system trust, study risks and benefits, altruism, knowledge generation, interference with clinical care, and placebos are key concerns and barriers for surrogate decision-makers to enroll patients in critical care trials. Future studies are needed to evaluate if charitable giving on the patient's behalf and public recognition are effective strategies to promote enrollment into critical care trials.

Computational investigation of outflow graft variation impact on hemocompatibility profile in LVADs.

BACKGROUND: Hemocompatibility-related adverse events (HRAE) occur commonly in patients with left ventricular assist devices (LVADs) and add to morbidity and mortality. It is unclear whether the outflow graft orientation can impact flow conditions leading to HRAE. This study presents a simulation-based approach using exact patient anatomy from medical images to investigate the influence of outflow cannula orientation in modulating flow conditions leading to HRAEs. METHODS: A 3D model of a proximal aorta and outflow graft was reconstructed from a computed tomography (CT) scan of an LVAD patient and virtually modified to model multiple cannula orientations (n = 10) by varying polar (cranio-caudal) (n = 5) and off-set (anterior-posterior) (n = 2) angles. Time-dependent computational flow simulations were then performed for each anatomical orientation. Qualitative and quantitative hemodynamics metrics of thrombogenicity including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), endothelial cell platelet activation potential (ECAP), particle residence time (PRT), and platelet activation potential (PLAP) were analyzed. RESULTS: Within the simulations performed, endothelial cell activation potential (ECAP) and particle residence time (PRT) were found to be lowest with a polar angle of 85°, regardless of offset angle. However, polar angles that produced parameters at levels least associated with thrombosis varied when the offset angle was changed from 0° to 12°. For offset angles of 0° and 12° respectively, flow shear was lowest at 65° and 75°, time averaged wall shear stress (TAWSS) was highest at 85° and 35°, and platelet activation potential (PLAP) was lowest at 65° and 45°. CONCLUSION: This study suggests that computational fluid dynamic modeling based on patient-specific anatomy can be a powerful analytical tool when identifying optimal positioning of an LVAD. Contrary to previous work, our findings suggest that there may be an "ideal" outflow cannula for each individual patient based on a CFD-based hemocompatibility profile.

The role of innovative modeling and imaging techniques in improving outcomes in patients with LVAD.

Heart failure remains a significant cause of mortality in the United States and around the world. While organ transplantation is acknowledged as the gold standard treatment for end stage heart failure, supply is limited, and many patients are treated with left ventricular assist devices (LVADs). LVADs extend and improve patients' lives, but they are not without their own complications, particularly the hemocompatibility related adverse events (HRAE) including stroke, bleeding and pump thrombosis. Mainstream imaging techniques currently in use to assess appropriate device function and troubleshoot complications, such as echocardiography and cardiac computed tomography, provide some insight but do not provide a holistic understanding of pump induced flow alterations that leads to HRAEs. In contrast, there are technologies restricted to the benchtop-such as computational fluid dynamics and mock circulatory loops paired with methods like particle image velocimetry-that can assess flow metrics but have not been optimized for clinical care. In this review, we outline the potential role and current limitations of converging available technologies to produce novel imaging techniques, and the potential utility in evaluating hemodynamic flow to determine whether LVAD patients may be at higher risk of HRAEs. This addition to diagnostic and monitoring capabilities could improve prevention and treatment of LVAD-induced complications in heart failure patients.

TGF-ß uncouples glycolysis and inflammation in macrophages and controls survival during sepsis.

Changes in metabolism of macrophages are required to sustain macrophage activation in response to different stimuli. We showed that the cytokine TGF-ß (transforming growth factor-ß) regulates glycolysis in macrophages independently of inflammatory cytokine production and affects survival in mouse models of sepsis. During macrophage activation, TGF-ß increased the expression and activity of the glycolytic enzyme PFKL (phosphofructokinase-1 liver type) and promoted glycolysis but suppressed the production of proinflammatory cytokines. The increase in glycolysis was mediated by an mTOR-c-MYC-dependent pathway, whereas the inhibition of cytokine production was due to activation of the transcriptional coactivator SMAD3 and suppression of the activity of the proinflammatory transcription factors AP-1, NF-κB, and STAT1. In mice with LPS-induced endotoxemia and experimentally induced sepsis, the TGF-ß-induced enhancement in macrophage glycolysis led to decreased survival, which was associated with increased blood coagulation. Analysis of septic patient cohorts revealed that the expression of PFKL, TGFBRI (which encodes a TGF-ß receptor), and F13A1 (which encodes a coagulation factor) in myeloid cells positively correlated with COVID-19 disease. Thus, these results suggest that TGF-ß is a critical regulator of macrophage metabolism and could be a therapeutic target in patients with sepsis.

Mucosal administration of a live attenuated recombinant COVID-19 vaccine protects nonhuman primates from SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein spike for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live, attenuated, recombinant human respiratory syncytial virus expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing by more than 200-fold the peak shedding of SARS-CoV-2 in the nose. MV-014-212 elicited mucosal immunoglobulin A in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against virus variants of concern Alpha, Beta, and Delta. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in Phase 1 clinical trials as an intranasal COVID-19 vaccine.

Cryo-EM structures reveal multiple stages of bacterial outer membrane protein folding.

Transmembrane ß barrel proteins are folded into the outer membrane (OM) of Gram-negative bacteria by the ß barrel assembly machinery (BAM) via a poorly understood process that occurs without known external energy sources. Here, we used single-particle cryo-EM to visualize the folding dynamics of a model ß barrel protein (EspP) by BAM. We found that BAM binds the highly conserved "ß signal" motif of EspP to correctly orient ß strands in the OM during folding. We also found that the folding of EspP proceeds via "hybrid-barrel" intermediates in which membrane integrated ß sheets are attached to the essential BAM subunit, BamA. The structures show an unprecedented deflection of the membrane surrounding the EspP intermediates and suggest that ß sheets progressively fold toward BamA to form a ß barrel. Along with in vivo experiments that tracked ß barrel folding while the OM tension was modified, our results support a model in which BAM harnesses OM elasticity to accelerate ß barrel folding.

"The Feasibility of Targeted Muscle Reinnervation for the Management of Morton's Neuroma".

BACKGROUND: Despite multiple surgical modalities available for the management of Morton's neuroma, complications remain common. Targeted muscle reinnervation (TMR) has yet to be explored as an option for the prevention of recurrence of Morton's neuroma. The purpose of the present investigation was to determine the consistency of the relevant foot neurovascular and muscle anatomy and to demonstrate the feasibility of TMR as an option for Morton's neuroma. METHODS: The anatomy of 5 fresh-tissue donor cadaver feet was studied, including the course and location of the medial and lateral plantar nerves (MPNs and LPNs), motor branches to abductor hallucis (AH) and flexor digitorum brevis (FDB), as well as the course of sensory plantar digital nerves. Measurements for the locations of the muscular and sensory branches were taken relative to landmarks including the navicular tuberosity (NT), AH, FDB, and the third metatarsophalangeal joint (third MTPJ). RESULTS: The mean number of nerve branches to FDB identified was 2. These branch points occurred at an average of 8.6 cm down the MPN or LPN, 9.0 cm from the third MTPJ, 3.0 cm distal to AH distal edge, and 4.8 cm from the NT. The mean number of nerves to AH was 2.2. These branch points occurred at an average of 6.3 cm down the MPN, 11.9 cm from the third MTPJ, 0.8 cm from the AH distal edge, and 3.8 cm from the NT. CONCLUSIONS: Recurrent interdigital neuroma, painful scar, and neuropathic pain are common complications of operative management for Morton's neuroma. Targeted muscle reinnervation is a technique that has demonstrated efficacy for the prevention and treatment of neuroma, neuropathic pain, and phantom limb pain in amputees. Herein, we have described the neuromuscular anatomy for the application of TMR for the management of Morton's neuroma. Target muscles, including the AH and FDB, have consistent innervation patterns in the foot, and consequently, TMR represents a viable option to consider for the management of recalcitrant Morton's neuroma. LEVELS OF EVIDENCE: V.

Lentzeacins A-E, New Bacterial-Derived 2,5- and 2,6-Disubstituted Pyrazines from a BGC-Rich Soil Bacterium Lentzea sp. GA3-008.

Pyrazines (1,4-diazirines) are an important group of natural products that have tremendous monetary value in the food and fragrance industries and can exhibit a wide range of biological effects including antineoplastic, antidiabetic and antibiotic activities. As part of a project investigating the secondary metabolites present in understudied and chemically rich Actinomycetes, we isolated a series of six pyrazines from a soil-derived Lentzea sp. GA3-008, four of which are new. Here we describe the structures of lentzeacins A-E (1, 3, 5 and 6) along with two known analogues (2 and 4) and the porphyrin zincphyrin. The structures were determined by NMR spectroscopy and HR-ESI-MS. The suite of compounds present in Lentzea sp. includes 2,5-disubstituted pyrazines (compounds 2, 4, and 6) together with the new 2,6-disubstituted isomers (compounds 1, 3 and 5), a chemical class that is uncommon. We used long-read Nanopore sequencing to assemble a draft genome sequence of Lentzea sp. which revealed the presence of 40 biosynthetic gene clusters. Analysis of classical di-modular and single module non-ribosomal peptide synthase genes, and cyclic dipeptide synthases narrows down the possibilities for the biosynthesis of the pyrazines present in this strain.

Genome-Guided Discovery of Natural Products through Multiplexed Low-Coverage Whole-Genome Sequencing of Soil Actinomycetes on Oxford Nanopore Flongle.

Genome mining is an important tool for discovery of new natural products; however, the number of publicly available genomes for natural product-rich microbes such as actinomycetes, relative to human pathogens with smaller genomes, is small. To obtain contiguous DNA assemblies and identify large (ca. 10 to greater than 100 kb) biosynthetic gene clusters (BGCs) with high GC (>70%) and high-repeat content, it is necessary to use long-read sequencing methods when sequencing actinomycete genomes. One of the hurdles to long-read sequencing is the higher cost. In the current study, we assessed Flongle, a recently launched platform by Oxford Nanopore Technologies, as a low-cost DNA sequencing option to obtain contiguous DNA assemblies and analyze BGCs. To make the workflow more cost-effective, we multiplexed up to four samples in a single Flongle sequencing experiment while expecting low-sequencing coverage per sample. We hypothesized that contiguous DNA assemblies might enable analysis of BGCs even at low sequencing depth. To assess the value of these assemblies, we collected high-resolution mass spectrometry data and conducted a multi-omics analysis to connect BGCs to secondary metabolites. In total, we assembled genomes for 20 distinct strains across seven sequencing experiments. In each experiment, 50% of the bases were in reads longer than 10 kb, which facilitated the assembly of reads into contigs with an average N50 value of 3.5 Mb. The programs antiSMASH and PRISM predicted 629 and 295 BGCs, respectively. We connected BGCs to metabolites for N,N-dimethyl cyclic-di-tryptophan, two novel lasso peptides, and three known actinomycete-associated siderophores, namely, mirubactin, heterobactin, and salinichelin. IMPORTANCE Short-read sequencing of GC-rich genomes such as those from actinomycetes results in a fragmented genome assembly and truncated biosynthetic gene clusters (often 10 to >100 kb long), which hinders our ability to understand the biosynthetic potential of a given strain and predict the molecules that can be produced. The current study demonstrates that contiguous DNA assemblies, suitable for analysis of BGCs, can be obtained through low-coverage, multiplexed sequencing on Flongle, which provides a new low-cost workflow ($30 to 40 per strain) for sequencing actinomycete strain libraries.

Respiratory Syncytial Virus Phosphoprotein Residue S156 Plays a Role in Regulating Genome Transcription and Replication.

Respiratory syncytial virus (RSV) is a single-stranded, negative-sense RNA virus in the family Pneumoviridae and genus Orthopneumovirus that can cause severe disease in infants, immunocompromised adults, and the elderly. The RSV viral RNA-dependent RNA polymerase (vRdRp) complex is composed of the phosphoprotein (P) and the large polymerase protein (L). The P protein is constitutively phosphorylated by host kinases and has 41 serine (S) and threonine (T) residues as potential phosphorylation sites. To identify important phosphorylation residues in the P protein, we systematically and individually mutated all S and T residues to alanine (A) and analyzed their effects on genome transcription and replication by using a minigenome system. We found that the mutation of eight residues resulted in minigenome activity significantly lower than that of wild-type (WT) P. We then incorporated these mutations (T210A, S203A, T151A, S156A, T160A, S23A, T188A, and T105A) into full-length genome cDNA to rescue recombinant RSV. We were able to recover four recombinant viruses (with T151A, S156A, T160A, or S23A), suggesting that RSV-P residues T210, S203, T188, and T105 are essential for viral RNA replication. Among the four recombinant viruses rescued, rRSV-T160A caused a minor growth defect relative to its parental virus while rRSV-S156A had severely restricted replication due to decreased levels of genomic RNA. During infection, P-S156A phosphorylation was decreased, and when passaged, the S156A virus acquired a known compensatory mutation in L (L795I) that enhanced both WT-P and P-S156A minigenome activity and was able to partially rescue the S156A viral growth defect. This work demonstrates that residues T210, S203, T188, and T105 are critical for RSV replication and that S156 plays a critical role in viral RNA synthesis. IMPORTANCE RSV-P is a heavily phosphorylated protein that is required for RSV replication. In this study, we identified several residues, including P-S156, as phosphorylation sites that play critical roles in efficient viral growth and genome replication. Future studies to identify the specific kinase(s) that phosphorylates these residues can lead to kinase inhibitors and antiviral drugs for this important human pathogen.

One mucosal administration of a live attenuated recombinant COVID-19 vaccine protects non-human primates from SARS-CoV-2

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein, spike, for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live attenuated, recombinant human respiratory syncytial virus (RSV) expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing by more than 200- fold the peak shedding of SARS-CoV-2 in the nose. MV-014-212 elicited mucosal immunity in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against two virus variants of concern. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in phase 1 clinical trials as a single-dose intranasal COVID-19 vaccine.

Structural Basis for a Dual Function ATP Grasp Ligase That Installs Single and Bicyclic ω-Ester Macrocycles in a New Multicore RiPP Natural Product.

Among the ribosomally synthesized and post-translationally modified peptide (RiPP) natural products, "graspetides" (formerly known as microviridins) contain macrocyclic esters and amides that are formed by ATP-grasp ligase tailoring enzymes using the side chains of Asp/Glu as acceptors and Thr/Ser/Lys as donors. Graspetides exhibit diverse patterns of macrocylization and connectivities exemplified by microviridins, that have a caged tricyclic core, and thuringin and plesiocin that feature a "hairpin topology" with cross-strand ω-ester bonds. Here, we characterize chryseoviridin, a new type of multicore RiPP encoded by Chryseobacterium gregarium DS19109 (Phylum Bacteroidetes) and solve a 2.44 Å resolution crystal structure of a quaternary complex consisting of the ATP-grasp ligase CdnC bound to ADP, a conserved leader peptide and a peptide substrate. HRMS/MS analyses show that chryseoviridin contains four consecutive five- or six-residue macrocycles ending with a microviridin-like core. The crystal structure captures respective subunits of the CdnC homodimer in the apo or substrate-bound state revealing a large conformational change in the B-domain upon substrate binding. A docked model of ATP places the γ-phosphate group within 2.8 Å of the Asp acceptor residue. The orientation of the bound substrate is consistent with a model in which macrocyclization occurs in the N- to C-terminal direction for core peptides containing multiple Thr/Ser-to-Asp macrocycles. Using systematically varied sequences, we validate this model and identify two- or three-amino acid templating elements that flank the macrolactone and are required for enzyme activity in vitro. This work reveals the structural basis for ω-ester bond formation in RiPP biosynthesis.

Factors associated with giving birth at advanced maternal age in the United States.

OBJECTIVE: In 2018, 17 percent of all births in the United States occurred to women of advanced maternal age (AMA.) While the outcomes of AMA pregnancies have been examined extensively, the drivers behind increasing rates of AMA pregnancies in the United States are less understood. Some scholars have asserted that women are increasingly delaying their first birth in favor of educational and career aspirations. Yet birth trends in the United States do not support this as the primary explanatory factor of AMA births. Other factors may also contribute to high rates of AMA in the United States. This study sought to identify main predictors of AMA birth using a cross-sectional retrospective sample. DESIGN: We employed a multivariate logistic regression analysis on a cross-sectional retrospective sample to identify significant independent predictors of giving birth at advance maternal age (AMA) in the United States. SETTING: Data was obtained from the Unites States Pregnancy Risk Assessment Monitoring System (PRAMS) Phase 7 Core Questionnaire and linked birth certificates. Questions are designed to assess maternal attitudes and experiences before, during and just after pregnancy. Surveys for Phase 7 were completed in 2017 and 2018. The study population represents mothers from 34 states that met the CDC's 55% response rate threshold and Puerto Rico. PARTICIPANTS: The PRAMS dataset comprises self-reported data and linked birth certificate data from women who recently gave birth. A total of 38,549 mothers are included in the Phase 7 dataset. State sample sizes ranged from 503 mothers in Wyoming to 1,897 mothers in Michigan. All mothers gave birth in the year 2017. MEASUREMENTS AND FINDINGS: The outcome of interest was AMA birth, defined as conceiving and subsequently giving birth to a baby at age 35 or older. Predictors for AMA birth were selected a priori and included: pregnancy intention, history of previous live birth, insurance status, income, education, race/ethnicity, marital status, and urban location. Previous live birth to at least one child was a significant independent predictor for AMA birth. Mothers with high parity, defined as 6 or more previous live births, were 17 times more likely to give birth at advanced maternal age. Mothers with an unwanted pregnancy were 1.9 times more likely to have an AMA birth. College attainment, high income, marital status, urbanicity, and race/ethnicity were also independent predictors of AMA birth. Health insurance was not a significant predictor of AMA birth after accounting for other factors. KEY CONCLUSIONS: Delayed and late childbirth may not be intentional for a significant group of older mothers. Converse to popular assumptions that women delay childbearing in favor of career aspirations, the majority of AMA mothers have previous children. Half of AMA mothers have two or more previous children. The findings in this paper suggests that multiple factors predict AMA births. There may be several subtypes of women who enter pregnancy at advanced maternal age. IMPLICATIONS FOR PRACTICE: As women weigh personal desire to bear children against competing social expectations, they may find themselves navigating their own unique path shaped in part by the region in which they live. Better characterization of the circumstances that lead to advanced maternal age in the United States, including exploration of unintended and unwanted AMA pregnancy, is necessary to develop policies and interventions that meet women's needs. This work should utilize a reproductive justice framework to ensure that women's preferences, particularly women of color, are upheld while promoting health and wellbeing for women.

Recombinant HA-based vaccine outperforms split and subunit vaccines in elicitation of influenza-specific CD4 T cells and CD4 T cell-dependent antibody responses in humans.

Although traditional egg-based inactivated influenza vaccines can protect against infection, there have been significant efforts to develop improved formats to overcome disadvantages of this platform. Here, we have assessed human CD4 T cell responses to a traditional egg-based influenza vaccine with recently available cell-derived vaccines and recombinant baculovirus-derived vaccines. Adults were administered either egg-derived Fluzone®, mammalian cell-derived Flucelvax® or recombinant HA (Flublok®). CD4 T cell responses to each HA protein were assessed by cytokine EliSpot and intracellular staining assays. The specificity and magnitude of antibody responses were quantified by ELISA and HAI assays. By all criteria, Flublok vaccine exhibited superior performance in eliciting both CD4 T cell responses and HA-specific antibody responses, whether measured by mean response magnitude or percent of responders. Although the mechanism(s) underlying this advantage is not yet clear, it is likely that both qualitative and quantitative features of the vaccines impact the response.

Factors associated with skin graft take in fibula and radial forearm free flap donor sites.

LEARNING OBJECTIVES: Identify factors associated with skin graft take in fibula free flaps (FFF) and radial forearm free flaps (RFFF) donor sites. STUDY OBJECTIVES: To determine which factors are associated with decreased skin graft take at the donor site in FFF and RFFF in head and neck patients. DESIGN: Retrospective Chart Review Case Series. SETTING: Multicenter Tertiary Care. METHODS: A multicenter retrospective review was performed at three institutions identifying patients who underwent free tissue transfer, specifically either FFF or RFFF, between 2007 and 2017. Patient demographics, medical history, and social history were examined including age, gender, BMI, smoking status, diabetes and preoperative anticoagulation use. Preoperative, intraoperative data, and postoperative data were also examined including tourniquet use, type of flap, area of skin graft, if the skin graft had a donor site or if it was taken from the flap, wound NPWT use, cast use, use of physical therapy, DVT prophylaxis, limb ischemia, heparin drip, and postoperative aspirin use. Statistical analysis was used to determine which factors were significantly associated with skin graft take. RESULTS: 1415 patients underwent a forearm or fibula flap and 938 patients underwent split-thickness skin graft. Of these, 592 patients had sufficient information and were included in the final analysis. There were 371 males and 220 females. The average age was 55.7. Complete skin graft take was seen in 480 patients (81.1%). On univariate analysis, patients with diabetes (p = .003), type of flap (fibula p < .001), skin graft area (p = .006), tourniquet use (p = .003), DVT prophylaxis (p = .008) and casting (p = .003) were significantly associated with decreased skin graft take rate. In a multivariate analysis, diabetes (OR 2.17 (95%CI 1.16-3.98)), fibula flaps (OR 2.86 (95%CI 1.79-4.76)), an increase in skin graft area (OR 1.01 (95%CI 1.01-1.01)), post-operative aspirin (OR 2.63 (95%CI 1.15-5.88), and casting (OR 2.94 (95%CI 1.22-7.14)) were associated with poor rates of skin graft take. CONCLUSION: Several factors affect skin graft take rate and should be considered when performing a skin graft for a donor site defect.

The Intersectionality of Leadership and Spiritual Development Through Mentoring.

Educational environments have the capacity to cultivate transformative leaders who can resolve global issues and move society toward a positive social change. This chapter focuses on the value of mentorship and community-based service projects to support students' spiritual and leadership development. Lessons learned via a university case study of intergenerational mentoring are included.

Tourniquet use and factors associated with hematoma formation in free tissue transfer.

PURPOSE: Our objective was to understand which variables are associated with hematoma formation at both the donor and recipient sites in head and neck free tissue transfer and if hematoma rates are affected by tourniquet use. METHODS: Patients were identified who underwent free tissue transfer at three institutions, specifically either a radial forearm free flap (RFFF) or a fibula free flap (FFF), between 2007 and 2017. Variables including use of tourniquet, anticoagulation, treatment factors, demographics, and post-operative factors were examined to see if they influenced hematoma formation at either the free tissue donor or recipient site. RESULTS: 1410 patients at three institutions were included in the analysis. There were 692 (49.1%) RFFF and 718 (50.9%) FFF. Tourniquets were used in 764 (54.1%) cases. There were 121 (8.5%) hematomas. Heparin drips (p < .001) and DVT prophylaxis (p = .03) were significantly associated with hematoma formation (OR 95% CI 12.23 (4.98-30.07), 3.46 (1.15-10.44) respectively) on multivariable analysis. CONCLUSIONS: Heparin Drips and DVT prophylaxis significantly increased hematoma rates in free flap patients while tourniquets did not affect rates of hematoma.

Congenital aneurysm of the palmar digital artery: A case report and literature review.

Spontaneous arterial aneurysms of the hand are uncommon but are well-described in the adult population. In the pediatric population, however, congenital or true aneurysms of the hand are exceptionally rare. A case report and a literature review were performed for published cases of arterial aneurysms of the hand in the pediatric population. A 13-month-old child presented with an aneurysm of the common digital artery and underwent surgical excision without need for reconstruction. Literature review found 13 documented cases. Patient characteristics and management strategies were summarized. There are very few documented cases of hand arterial aneurysms in the pediatric population, with our patient being the third youngest ever reported. No cases were associated with hereditary disease, and aneurysm excision was performed in all cases. Our report highlights the need to include arterial aneurysm in a differential diagnosis when evaluating a pediatric patient with a palpable hand mass.

YbtT is a low-specificity type II thioesterase that maintains production of the metallophore yersiniabactin in pathogenic enterobacteria.

Clinical isolates of Yersinia, Klebsiella, and Escherichia coli frequently secrete the small molecule metallophore yersiniabactin (Ybt), which passivates and scavenges transition metals during human infections. YbtT is encoded within the Ybt biosynthetic operon and is critical for full Ybt production in bacteria. However, its biosynthetic function has been unclear because it is not essential for Ybt production by the in vitro reconstituted nonribosomal peptide synthetase/polyketide synthase (NRPS/PKS) pathway. Here, we report the structural and biochemical characterization of YbtT. YbtT structures at 1.4-1.9 Å resolution possess a serine hydrolase catalytic triad and an associated substrate chamber with features similar to those previously reported for low-specificity type II thioesterases (TEIIs). We found that YbtT interacts with the two major Ybt biosynthetic proteins, HMWP1 (high-molecular-weight protein 1) and HMWP2 (high-molecular-weight protein 2), and hydrolyzes a variety of aromatic and acyl groups from their phosphopantetheinylated carrier protein domains. In vivo YbtT titration in uropathogenic E. coli revealed a distinct optimum for Ybt production consistent with a tradeoff between clearing both stalled inhibitory intermediates and productive Ybt precursors from HMWP1 and HMWP2. These results are consistent with a model in which YbtT maintains cellular Ybt biosynthesis by removing nonproductive, inhibitory thioesters that form aberrantly at multiple sites on HMWP1 and HMWP2.