A national census for the off-label treatment of complex aortic aneurysms.

OBJECTIVE: Despite regulatory challenges, device availability, and rapidly expanding techniques, off-label endovascular repair of complex aortic aneurysms (cAAs) has expanded in the past decade. Given the lack of United States Food and Drug Administration-approved endovascular technology to treat cAAs, we performed a national census to better understand volume and current practice patterns in the United States. METHODS: Targeted sampling identified vascular surgeons with experience in off-label endovascular repair of cAAs. An electronic survey was distributed with institutional review board approval from the University of Rochester to 261 individuals with a response rate of 38% (n = 98). RESULTS: A total of 93 respondents (95%) reported off-label endovascular repair of cAAs. Mean age was 45.7 ± 8.3 years, and 84% were male. Most respondents (59%) were within the first 10 years of practice, and 69% trained at institutions with a high-volume of off-label endovascular procedures for complex aortic aneurysms with or without a physician-sponsored investigational device exemption (PS-IDE). Twelve respondents from 11 institutions reported institutional PS-IDEs for physician-modified endografts (PMEGs), in-situ laser fenestration (ISLF), or parallel grafting technique (PGT), including sites with PS-IDEs for custom-manufactured devices. Eighty-nine unique institutions reported elective off-label endovascular repair with a mean of 20.2 ± 16.5 cases/year and ∼1757 total cases/year nationally. Eighty reported urgent/emergent off-label endovascular repair with a mean of 5.7 ± 5.4 cases/year and ∼499 total cases/year nationally. There was no correlation between high-volume endovascular institutions (>15 cases/year) and institutions with high volumes of open surgical repair for cAAs (>15 cases/year; odds ratio, 0.7; 95% confidence interval, 0.3-1.5; P = .34). Elective techniques included PMEG (70%), ISLF (30%), hybrid PMEG/ISLF (18%), and PGT (14%), with PMEG being the preferred technique for 63% of respondents. Techniques for emergent endovascular treatment of complex aortic disease included PMEG (52%), ISLF (40%), PGT (20%), and hybrid-PMEG/ISLF (14%), with PMEG being the preferred technique for 41% of respondents. Thirty-nine percent of respondents always or frequently offer referrals to institutions with PS-IDEs for custom-manufactured devices. The most common barrier for referral to PS-IDE centers included geographic distance (48%), longitudinal relationship with patient (45%), and costs associated with travel (33%). Only 61% of respondents participate in the Vascular Quality Initiative for complex endovascular aneurysm repair, and only 57% maintain a prospective institutional database. Eighty-six percent reported interest in a national collaborative database for off-label endovascular repair of cAA. CONCLUSIONS: Estimates of off-label endovascular repair of cAAs are likely underrepresented in the literature based on this national census. PMEG was the most common technique for elective and emergent procedures. Under-reported off-label endovascular repair of cAA outcomes data appears to be limited by non-standardized PS-IDE reporting to the United States Food and Drug Administration, and the lack of Vascular Quality Initiative participation and prospective institutional data collection. Most participants are interested in a national collaborative database for endovascular repair of cAAs.

Early Financial Outcomes of Physician Modified Endograft Programs Are Dictated by Device Cost.

INTRODUCTION: Physician-modified endografts (PMEGs) have been used for repair of thoracoabdominal aortic aneurysms (TAAAs) for 2 decades with good outcomes but limited financial data. This study compared the financial and clinical outcomes of PMEGs to the Cook Zenith-Fenestrated (ZFEN) graft and open surgical repair (OSR). METHODS: A retrospective review of financial and clinical data was performed for all patients who underwent endovascular or OSR of juxtarenal aortic aneurysms and TAAAs from January 2018 to December 2022 at an academic medical center. Clinical presentation, demographics, operative details, and outcomes were reviewed. Financial data was obtained through the institution's finance department. The primary end point was contribution margin (CM). RESULTS: Thirty patients met inclusion criteria, consisting of twelve PMEG, seven ZFEN, and eleven open repairs. PMEG repairs had a total CM of -$110,000 compared to $18,000 for ZFEN and $290,000 for OSR. Aortic and branch artery implants were major cost-drivers for endovascular procedures. Extent II TAAA repairs were the costliest PMEG procedure, with a total device cost of $59,000 per case. PMEG repairs had 30-d and 1-y mortality rates of 8.3% which was not significantly different from ZFEN (0.0%, P = 0.46; 0.0%, P = 0.46) or OSR (9.1%, P = 0.95; 18%, P = 0.51). Average intensive care unit and hospital stay after PMEG repairs were comparable to ZFEN and shorter than OSR. CONCLUSIONS: Our study suggests that PMEG repairs yield a negative CM. To make these cases financially viable for hospital systems, device costs will need to be reduced or reimbursement rates increased by approximately $8800.

Feasibility of an Open Dialogue-Inspired Approach for Young Adults with Psychosis in a Public Hospital System.

The objective was to determine the feasibility of an Open Dialogue-inspired approach in a metropolitan, public hospital setting with predominately African American participants. Participants were ages 18-35, experienced psychosis within the past month, and involved at least one support person in their care. We evaluated domains of feasibility including implementation, adaptation, practicality, acceptability, and limited-efficacy. An organizational change model (Addressing Problems Through Organizational Change) facilitated implementation. Clinicians received three trainings and ongoing supervision. Network meetings were successfully implemented with good self-reported fidelity to principles of dialogic practice. Some adaptations (less frequent meetings and no home visits) were necessary. A subset of individuals completed research assessments over 12 months. Qualitative interviews with participants suggested the intervention was acceptable. Symptom and functional outcomes were preliminary but trended toward improvement. Implementation was feasible with relatively brief training, organizational change processes, and context-specific adaptations. Lessons learned can assist in planning a larger research study.

Engineered Chimeras Unveil Swappable Modular Features of Fatty Acid and Polyketide Synthase Acyl Carrier Proteins.

The strategic redesign of microbial biosynthetic pathways is a compelling route to access molecules of diverse structure and function in a potentially environmentally sustainable fashion. The promise of this approach hinges on an improved understanding of acyl carrier proteins (ACPs), which serve as central hubs in biosynthetic pathways. These small, flexible proteins mediate the transport of molecular building blocks and intermediates to enzymatic partners that extend and tailor the growing natural products. Past combinatorial biosynthesis efforts have failed due to incompatible ACP-enzyme pairings. Herein, we report the design of chimeric ACPs with features of the actinorhodin polyketide synthase ACP (ACT) and of the Escherichia coli fatty acid synthase (FAS) ACP (AcpP). We evaluate the ability of the chimeric ACPs to interact with the E. coli FAS ketosynthase FabF, which represents an interaction essential to building the carbon backbone of the synthase molecular output. Given that AcpP interacts with FabF but ACT does not, we sought to exchange modular features of ACT with AcpP to confer functionality with FabF. The interactions of chimeric ACPs with FabF were interrogated using sedimentation velocity experiments, surface plasmon resonance analyses, mechanism-based cross-linking assays, and molecular dynamics simulations. Results suggest that the residues guiding AcpP-FabF compatibility and ACT-FabF incompatibility may reside in the loop I, α-helix II region. These findings can inform the development of strategic secondary element swaps that expand the enzyme compatibility of ACPs across systems and therefore represent a critical step toward the strategic engineering of "un-natural" natural products.

Thirty-year single-center experience with arterial thoracic outlet syndrome.

OBJECTIVE: Arterial thoracic outlet syndrome (ATOS) is rare. We present our 30-year experience with the management of ATOS at a high-volume referral center. METHODS: A retrospective review of all patients who had undergone primary operative treatment for ATOS from 1988 to 2018 was performed. ATOS was defined as subclavian artery pathology caused by extrinsic compression from a bony abnormality within the thoracic outlet. RESULTS: A total of 41 patients (45 limbs) underwent surgery for ATOS at a median age of 46 years (interquartile range [IQR], 34-58 years). Chronic symptoms (>6 weeks) were present in 31 limbs (69%). Of the 45 limbs, 13 (29%) presented with acute limb ischemia (ALI), requiring urgent brachial artery thromboembolectomy (BAT) in 9 and catheter-directed thrombolysis and thrombectomy (CDT) in 4. All patients underwent thoracic outlet decompression. 31 limbs (69%) required subclavian artery reconstruction. No perioperative deaths and only one major adverse limb event occurred. Patients with ALI underwent staged thoracic outlet decompression after initial BAT or CDT at a median of 23 days (IQR, 11-140 days). Of the 13 limbs with an initial presentation of ALI, 8 (62%) had recurrent thromboembolic events before thoracic outlet decompression subsequently requiring 10 additional BATs and 1 CDT. The cumulative probability of recurrent embolization at 14, 30, and 90 days was 8.33% (95% confidence interval [CI], 1.28%-54.42%), 16.67% (95% CI, 4.70%-59.06%), and 33.33% (95% CI, 14.98-74.20%), respectively. The median follow-up for 32 patients (35 limbs) was 13 months (IQR, 5-36 months). Subclavian artery/graft primary and secondary patency was 87% and 90%, respectively, at 5 years by Kaplan-Meier analysis. Of the 35 limbs, 5 (14%) had chronic upper extremity pain and 5 (14%) had persistent weakness. Preoperative forearm or hand pain and brachial artery occlusion were associated with chronic pain (P = .04 and P = .03) and weakness (P = .03 and P = .02). Of the 13 limbs that presented with ALI, 11 had a median follow-up after thoracic outlet decompression of 6 months (IQR, 5-14 months), including 9 (82%) with oral anticoagulation therapy. Anticoagulation therapy had no effect on subclavian artery patency (P = 1.0) or the presence of chronic symptoms (P = .93). CONCLUSIONS: The presentation of ATOS is diverse, and the diagnosis can be delayed. Preoperative upper extremity pain and brachial artery occlusion in the setting of ALI were associated with chronic pain and weakness after thoracic outlet decompression. Delayed thoracic outlet decompression was associated with an increased risk of recurrent thromboembolic events for patients who presented with ALI. An early and accurate diagnosis of ATOS is necessary to reduce morbidity and optimize outcomes.

Aneurysms of the superior mesenteric artery and its branches.

OBJECTIVE: Aneurysms of the superior mesenteric artery (SMA) and its branches are rare and account for only 6% to 15% of all visceral artery aneurysms. In the present report, we have described our 30-year experience with the management of aneurysms of the SMA and its branches at a high-volume referral center. METHODS: A retrospective review of all patients with a diagnosis of an aneurysm of the SMA or one of its branches from 1988 to 2018 was performed. Pseudoaneurysms and mycotic aneurysms were excluded. The clinical presentation, etiology, aneurysm shape and size, treatment modalities, and outcomes were analyzed. The growth rate of the aneurysms was estimated using linear regression. RESULTS: A total of 131 patients with 144 aneurysms were reviewed. The patients were primarily men (64%), with a median age of 60 years. Of the 144 aneurysms, 57 were fusiform, 30 were saccular, and 57 were dissection-associated aneurysms. Of the 131 patients, 41 had had an isolated SMA branch aneurysm. Degenerative aneurysms were the most common etiology (66%). A total of 35 patients (27%) were symptomatic at presentation. Of the 144 aneurysms, 111 had multiple computed tomography angiograms available, with a median follow-up of 43.6 months (interquartile range, 10.6-87.2 months). Only 18 aneurysms (16%) had had an estimated growth rate of ≥1.0 mm/y. The initial aneurysm size was significantly associated with the growth rate for the fusiform aneurysms (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.0-1.3]; P = .02) but not for the saccular (OR, 0.91; 95% CI, 0.76-1.1; P = 1.1) or dissection-associated (OR, 1.2; 95% CI, 0.91-1.5; P = .20) aneurysms. Acute abdominal pain (OR, 5.9; 95% CI, 1.6-22; P = .01) and chronic abdominal pain (OR, 3.7; 95% CI, 1.1-13; P = .04) were associated with aneurysm growth. Only two patients had a ruptured aneurysm, both of whom presented with rupture with no prior imaging studies. These two patients had a diagnosis of fibromuscular dysplasia and systemic lupus erythematosus, respectively. Of the 131 patients, 46 (34%) had undergone operative repair, including 36 open revascularizations and 8 endovascular procedures. The average aneurysm size for these 46 patients was 24.0 ± 8.6 mm. One patient died perioperatively, and nine patients experienced perioperative complications (25%). Of the 144 aneurysms, 91 were <20 mm, with an average size of 13.4 ± 3.1 mm. These 91 aneurysms had been followed up for a median of 120.8 months (interquartile range, 30.5-232.2 months), with no ruptures within this cohort during the follow-up period. CONCLUSIONS: The present study represents one of the largest series on aneurysms of the SMA and its branches. Our results showed that aneurysms of the SMA are relatively stable. Patients with symptomatic and fusiform aneurysms had a greater risk of growth. Aneurysms <20 mm with a degenerative etiology can be safely monitored without treatment.

Influence of Ligand Structure on Excited State Surface Chemistry of Lead Sulfide Quantum Dots.

The ligand-nanocrystal boundaries of colloidal quantum dots (QDs) mediate the primary energy and electron transfer processes that underpin photochemical and photocatalytic transformations at their surfaces. We use mid-infrared transient absorption spectroscopy to reveal the influence that ligand structure and bonding to nanocrystal surfaces have on the changes of the excited state surface chemistry of this boundary in PbS QDs and the corresponding impact on charge transfer processes between nanocrystals. We demonstrate that oleate ligands undergo marked changes in their bonding to surfaces in the excitonic excited states of the nanocrystals, indicating that oleate passivated PbS surfaces undergo significant structural changes following photoexcitation. These changes can impact the surface mobility of the ligands and the ability of redox shuttles to approach the nanocrystal surfaces to undergo charge transfer in photocatalytic reactions. In contrast, markedly different transient vibrational features are observed in iodide/mercaptoproprionic acid passivated PbS QD films that result from charge transfer between neighboring nanocrystals and localization of holes at the nanocrystal surfaces near MPA ligands. This ability to distinguish the influence that excitonic excited states vs charge transfer processes have on the surface chemistry of the ligand-nanocrystal boundary lays the groundwork for exploration of how this boundary can be understood and controlled for the design of nanocrystalline materials tailored for specific applications in solar energy harvesting and photocatalytic reactions.

Are Vascular Surgery Trainees Satisfied and are They Using the Right Factors to Choose a Training Program?

BACKGROUND: Medical students and residents often evaluate training sites in vascular surgery with minimal exposure to those programs. We sought to identify factors associated with vascular surgery trainee satisfaction in relation to their current work environment and how they made their rank list. METHODS: All integrated residents and fellows currently in United States vascular training programs were queried using an anonymous electronic survey for variables of their current training environment, factors that influenced their rank order list, and satisfaction. Questions were graded on a Likert scale. Continuous, ordinal, and categorical variables were respectively analyzed using the two-sample t-test, Mann-Whitney U-test/Wilcoxon rank sum test, and Fisher's exact test. RESULTS: A total of 166 of 517 (32%) trainees completed the survey with equal distribution across postgraduate years. Respondents reported high rates of satisfaction with their training program overall (84%), including 88% (n = 83) of residents and 78% (n = 56) of fellows. Several work environment variables were associated with both resident and fellow satisfaction including program-funded trips for conferences and presentations (P = 0.027 for residents; P = 0.001 for fellows), diversity of operative cases (P = 0.024; P < 0.001), perception of a strong supportive social network at the hospital (P = 0.006; P = 0.001), and perception of appreciation by attending surgeons (P < 0.001; P < 0.001). Fellows who felt appreciated by nursing staff (P = 0.047), ancillary staff (P = 0.013), and patients were more likely to be satisfied (P = 0.011); however, this was not true for integrated residents. Social outings with nontrainee family and friends were associated with satisfaction for fellows (P = 0.002) but not integrated residents (P = 0.138), whereas social outings with vascular trainees were associated with satisfaction for integrated residents (P = 0.047) but not fellows (P = 0.375). Similarly, satisfied integrated residents were more likely to have close relationships with their vascular cotrainees (P = 0.035) than fellows (P = 0.349). No rank list factors were found to be predictive of current trainee satisfaction for integrated residents. Rank list factors associated with fellow satisfaction included recommendation of the institution from a mentor (P < 0.001), success of program graduates (P = 0.002), faculty (P = 0.014), perceived program prestige (P = 0.040), and amount of early operative exposure (P = 0.042). CONCLUSIONS: Vascular surgery trainees report a high level of satisfaction with their training program. Fellow satisfaction was more dependent on the perception of their workplace peers than integrated residents. Satisfied integrated residents were more likely to have close relationships with their vascular cotrainees than fellows.

Vibrational probe of the origin of singlet exciton fission in TIPS-pentacene solutions.

We use native vibrational modes of the model singlet fission chromophore 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-Pn) to examine the origins of singlet fission in solution between molecules that are not tethered by a covalent linkage. We use the C-H stretch modes of TIPS side groups of TIPS-Pn to demonstrate that singlet fission does not occur by diffusive encounter of independent molecules in solution. Instead, TIPS-Pn molecules aggregate in solution through their TIPS side groups. This aggregation breaks the symmetry of the TIPS-Pn molecules and enables the formation of triplets to be probed through the formally symmetry forbidden symmetric alkyne stretch mode of the TIPS side groups. The alkyne stretch modes of TIPS-Pn are sensitive to the electronic excited states present during the singlet fission reaction and provide unique signatures of the formation of triplets following the initial separation of triplet pair intermediates. These findings highlight the opportunity to leverage structural information from vibrational modes to better understand intermolecular interactions that lead to singlet fission.

Using molecular vibrations to probe exciton delocalization in films of perylene diimides with ultrafast mid-IR spectroscopy.

Ultrafast vibrational spectroscopy in the mid-infrared was used to directly probe the delocalization of excitons in two different perylenediimide (PDI) derivatives that are predicted to preclude the formation of excimers, which can act as trap sites for excited state energy in organic semiconductors. We identified vibrational modes within the conjugated C-C stretch modes of PDI molecules whose frequencies reported the interactions of molecules within delocalized excitonic states. The vibrational linewidths of these modes, which we call intermolecular coordinate coupled (ICC) modes, provided a direct probe of the extent of exciton delocalization among the PDI molecules, which was confirmed using X-ray diffraction and electro-absorption spectroscopy. We show that a slip-stacked geometry among the PDI molecules in their crystals promotes delocalized charge-transfer (CT) excitons, while localized Frenkel excitons tend to form in crystals with helical, columnar stacking geometries. Because all molecules possess vibrational modes, the use of ultrafast mid-infrared spectroscopy to measure ICC vibrational modes offers a new approach to examine exciton delocalization in a variety of small molecule electron acceptors for optoelectronic and organic photovoltaic applications.

Dynamic Exchange During Triplet Transport in Nanocrystalline TIPS-Pentacene Films.

The multiplication of excitons in organic semiconductors via singlet fission offers the potential for photovoltaic cells that exceed the Shockley-Quiesser limit for single-junction devices. To fully utilize the potential of singlet fission sensitizers in devices, it is necessary to understand and control the diffusion of the resultant triplet excitons. In this work, a new processing method is reported to systematically tune the intermolecular order and crystalline structure in films of a model singlet fission chromophore, 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-Pn), without the need for chemical modifications. A combination of transient absorption spectroscopy and quantitative materials characterization enabled a detailed examination of the distance- and time-dependence of triplet exciton diffusion following singlet fission in these nanocrystalline TIPS-Pn films. Triplet-triplet annihilation rate constants were found to be representative of the weighted average of crystalline and amorphous phases in TIPS-Pn films comprising a mixture of phases. Adopting a diffusion model used to describe triplet-triplet annihilation, the triplet diffusion lengths for nanocrystalline and amorphous films of TIPS-Pn were estimated to be ∼75 and ∼14 nm, respectively. Importantly, the presence of even a small fraction (<10%) of the amorphous phase in the TIPS-Pn films greatly decreased the ultimate triplet diffusion length, suggesting that pure crystalline materials may be essential to efficiently harvest multiplied triplets even when singlet fission occurs on ultrafast time scales.

Programming Dynamic Division of Labor Using Horizontal Gene Transfer.

The metabolic engineering of microbes has broad applications, including biomanufacturing, bioprocessing, and environmental remediation. The introduction of a complex, multistep pathway often imposes a substantial metabolic burden on the host cell, restraining the accumulation of productive biomass and limiting pathway efficiency. One strategy to alleviate metabolic burden is the division of labor (DOL) in which different subpopulations carry out different parts of the pathway and work together to convert a substrate into a final product. However, the maintenance of different engineered subpopulations is challenging due to competition and convoluted interstrain population dynamics. Through modeling, we show that dynamic division of labor (DDOL), which we define as the DOL between indiscrete populations capable of dynamic and reversible interchange, can overcome these limitations and enable the robust maintenance of burdensome, multistep pathways. We propose that DDOL can be mediated by horizontal gene transfer (HGT) and use plasmid genomics to uncover evidence that DDOL is a strategy utilized by natural microbial communities. Our work suggests that bioengineers can harness HGT to stabilize synthetic metabolic pathways in microbial communities, enabling the development of robust engineered systems for deployment in a variety of contexts.

Strategies to reduce rates of severe endothermal heat-induced thrombosis following radiofrequency ablation.

OBJECTIVE: Endothermal heat-induced thrombosis (EHIT) is a potential complication of radiofrequency ablation (RFA). Data on effective prophylaxis of EHIT are limited. In 2018, a high-volume, single institution implemented strategies to decrease the incidence of EHIT, including a single periprocedural prophylactic dose of low-molecular-weight heparin to patients with a great saphenous vein (GSV) diameter of ≥8 mm or saphenofemoral junction (SFJ) diameter of ≥10 mm and limiting treatment to one vein per procedure. The size threshold was derived from existing literature. The study objective was to evaluate the effects of these institutional changes on thrombotic complication rates after RFA. METHODS: A retrospective cohort control study was conducted using the Vascular Quality Initiative database. Data were collected for patients who underwent RFA with a GSV diameter of ≥8 mm or SFJ diameter of ≥10 mm from January 2015 to July 2022. The clinical end points were thrombotic complications (ie, thrombophlebitis, EHIT, deep vein thrombosis) and bleeding complications. Patient demographic and procedural variables were included in the analysis, and significant variables after univariable logistic regression were included in a multivariable logistic regression. RESULTS: After the policy change, the overall vein center EHIT rate decreased from 2.6% to 1.5%, with a trend toward significance (P = .096). The inclusion criterion of a GSV diameter of ≥8 mm or an SFJ diameter of ≥10 mm yielded 845 patients, of whom 298 were treated before the policy change and 547 after. There was a significant reduction in the rate of EHIT classified as class ≥III (2.34 vs 0.366; P = .020) after the institutional changes. Treatment of two or more veins and an increased vein diameter were associated with an increased risk of EHIT (P = .049 and P < .001, respectively). No significant association was found between periprocedural anticoagulation and all-cause thrombotic complications or EHIT (P = .563 and P = .885, respectively). CONCLUSIONS: The institutional policy changes have led to lower rates of EHIT, with a reduction in severe EHIT rates in patients with an ≥8-mm diameter GSV or a ≥10-mm diameter SFJ treated with RFA. Of the changes implemented, restricting treatment to one vein was associated with a reduction in severe EHIT. No association was found with periprocedural low-molecular-weight heparin, although a type 2 error might have occurred. Alternative strategies to prevent thrombotic complications should be explored, such as increasing the dosage and duration of periprocedural anticoagulation, antiplatelet use, and nonpharmacologic strategies.

Duplicated antibiotic resistance genes reveal ongoing selection and horizontal gene transfer in bacteria.

Horizontal gene transfer (HGT) and gene duplication are often considered as separate mechanisms driving the evolution of new functions. However, the mobile genetic elements (MGEs) implicated in HGT can copy themselves, so positive selection on MGEs could drive gene duplications. Here, we use a combination of modeling and experimental evolution to examine this hypothesis and use long-read genome sequences of tens of thousands of bacterial isolates to examine its generality in nature. Modeling and experiments show that antibiotic selection can drive the evolution of duplicated antibiotic resistance genes (ARGs) through MGE transposition. A key implication is that duplicated ARGs should be enriched in environments associated with antibiotic use. To test this, we examined the distribution of duplicated ARGs in 18,938 complete bacterial genomes with ecological metadata. Duplicated ARGs are highly enriched in bacteria isolated from humans and livestock. Duplicated ARGs are further enriched in an independent set of 321 antibiotic-resistant clinical isolates. Our findings indicate that duplicated genes often encode functions undergoing positive selection and horizontal gene transfer in microbial communities.

Gore TAG thoracic branch endograft for treatment of a subacute type B aortic dissection complicated by rupture.

An 80-year-old man presented with a subacute zone 3-5 type B aortic dissection complicated by rupture and visceral and lower extremity malperfusion. He underwent emergent zone 2 repair with a Gore TAG thoracic branch endograft with inclusion of the left subclavian artery for a dominant left vertebral artery. The patient's postoperative course was uncomplicated. Type B aortic dissections can be anatomically complex, and rupture is a rare complication in the subacute phase. We report the novel use of a Gore TAG thoracic branch endograft for the management of type B aortic dissection complicated by rupture and demonstrate its feasibility for patients with type B aortic dissection complicated by rupture.

Programming dynamic division of labor using horizontal gene transfer.

The metabolic engineering of microbes has broad applications, including in biomanufacturing, bioprocessing, and environmental remediation. The introduction of a complex, multi-step pathway often imposes a substantial metabolic burden on the host cell, restraining the accumulation of productive biomass and limiting pathway efficiency. One strategy to alleviate metabolic burden is division of labor (DOL), in which different subpopulations carry out different parts of the pathway and work together to convert a substrate into a final product. However, the maintenance of different engineered subpopulations is challenging due to competition and convoluted inter-strain population dynamics. Through modeling, we show that dynamic division of labor (DDOL) mediated by horizontal gene transfer (HGT) can overcome these limitations and enable the robust maintenance of burdensome, multi-step pathways. We also use plasmid genomics to uncover evidence that DDOL is a strategy utilized by natural microbial communities. Our work suggests that bioengineers can harness HGT to stabilize synthetic metabolic pathways in microbial communities, enabling the development of robust engineered systems for deployment in a variety of contexts.

Heterologous Expression, Purification, and Characterization of Type II Polyketide Synthase Acyl Carrier Proteins.

The enzymes that comprise type II polyketide synthases (PKSs) are powerful biocatalysts that, once well-understood and strategically applied, could enable cost-effective and sustainable access to a range of pharmaceutically relevant molecules. Progress toward this goal hinges on gaining ample access to materials for in vitro characterizations and structural analysis of the components of these synthases. A central component of PKSs is the acyl carrier protein (ACP), which serves as a hub during the biosynthesis of type II polyketides. Herein, we share methods for accessing type II PKS ACPs via heterologous expression in E. coli . We also share how the installation of reactive and site-specific spectroscopic probes can be leveraged to study the conformational dynamics and interactions of type II PKS ACPs.

Building Bridges Between Evidence and Policy in Mental Health Services Research: Introducing the Policy Review Article Type.

Although it is widely accepted that patients do better when evidence-based health care practices are used, there is less acknowledgment of the positive outcomes associated with evidence-based policy making. To address the need for high-quality evidence to inform mental health policies, Psychiatric Services has recently launched a new article format: the Policy Review. This review type defines a specific policy-relevant issue affecting behavioral health systems, describes current knowledge and limitations, and discusses policy implications. Reviews can focus on mental health policies or examine how other health or social policies affect people with mental illness or substance use disorders. This brief overview of the need for a policy review article type describes differences between evidence-based policy making and practices and looks at research approaches focused on evidence-based policy making, as well as legislative and other efforts to support it. Broad guidelines for potential submissions are also provided.

Access to Burn Care in Low- and Middle-Income Countries: An Assessment of Timeliness, Surgical Capacity, and Affordability in a Regional Referral Hospital in Tanzania.

This study investigates patients' access to surgical care for burns in a low- and middle-income setting by studying timeliness, surgical capacity, and affordability. A survey was conducted in a regional referral hospital in Manyara, Tanzania. In total, 67 patients were included. To obtain information on burn victims in need of surgical care, irrespective of time lapsed from the burn injury, both patients with burn wounds and patients with contractures were included. Information provided by patients and/or caregivers was supplemented with data from patient files and interviews with hospital administration and physicians. In the burn wound group, 50% reached a facility within 24 hours after the injury. Referrals from other health facilities to the regional referral hospital were made within 3 weeks for 74% in this group. Of contracture patients, 74% had sought healthcare after the acute burn injury. Of the same group, only 4% had been treated with skin grafts beforehand, and 70% never received surgical care or a referral. Together, both groups indicated that lack of trust, surgical capacity, and referral timeliness were important factors negatively affecting patient access to surgical care. Accounting for hospital fees indicated patients routinely exceeded the catastrophic expenditure threshold. It was determined that healthcare for burn victims is without financial risk protection. We recommend strengthening burn care and reconstructive surgical programs in similar settings, using a more comprehensive health systems approach to identify and address both medical and socioeconomic factors that determine patient mortality and disability.

Myelin-specific T cells in animals with Japanese macaque encephalomyelitis.

OBJECTIVE: To determine whether animals with Japanese macaque encephalomyelitis (JME), a spontaneous demyelinating disease similar to multiple sclerosis (MS), harbor myelin-specific T cells in their central nervous system (CNS) and periphery. METHODS: Mononuclear cells (MNCs) from CNS lesions, cervical lymph nodes (LNs) and peripheral blood of Japanese macaques (JMs) with JME, and cervical LN and blood MNCs from healthy controls or animals with non-JME conditions were analyzed for the presence of myelin-specific T cells and changes in interleukin 17 (IL-17) and interferon gamma (IFNγ) expression. RESULTS: Demyelinating JME lesions contained CD4+ T cells and CD8+ T cells specific to myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and/or proteolipid protein (PLP). CD8+ T-cell responses were absent in JME peripheral blood, and in age- and sex-matched controls. However, CD4+ Th1 and Th17 responses were detected in JME peripheral blood versus controls. Cervical LN MNCs from eight of nine JME animals had CD3+ T cells specific for MOG, MBP, and PLP that were not detected in controls. Mapping myelin epitopes revealed a heterogeneity in responses among JME animals. Comparison of myelin antigen sequences with those of JM rhadinovirus (JMRV), which is found in JME lesions, identified six viral open reading frames (ORFs) with similarities to myelin antigen sequences. Overlapping peptides to these JMRV ORFs did not induce IFNγ responses. INTERPRETATIONS: JME possesses an immune-mediated component that involves both CD4+ and CD8+ T cells specific for myelin antigens. JME may shed new light on inflammatory demyelinating disease pathogenesis linked to gamma-herpesvirus infection.