Gossiping the (recipient's) day away: The impact of supervisor-directed gossip on recipients' rumination, sleep quality, vitality, and work outcomes.

Despite gossip research's predominant focus on gossipers and gossip targets, existing theoretical views and the limited yet important empirical studies converge to suggest that gossip benefits its recipients. Our research builds on conservation of resources theory to shift this consensus by examining the negative effects of supervisor-directed gossip on recipients. We theorize that hearing negative supervisor-directed gossip triggers both cognition- and affect-focused rumination, which consume resources, and we develop a research question around the moderating role of hearing positive supervisor-directed gossip. Furthermore, we propose that the aforementioned effects have cascading implications for recipients' work behaviors the following day. In a 15-day experience sampling investigation of 122 workers, we found that on days when employees hear negative gossip about the supervisor, they are more likely to engage in cognition- and affect-focused rumination, and hearing positive supervisor-directed gossip strengthens these positive relationships. In addition, we found that cognition- and affect-focused rumination lead to poor sleep quality and diminished next-morning vitality, which in turn results in reduced work engagement and supervisor-directed organizational citizenship behavior. We conclude by discussing the implications and future directions of our work. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Ribosomal protein control of hematopoietic stem cell transformation through direct, non-canonical regulation of metabolism.

We report here that expression of the ribosomal protein, RPL22, is frequently reduced in human myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML); reduced RPL22 expression is associated with worse outcomes. Mice null for Rpl22 display characteristics of an MDS-like syndrome and develop leukemia at an accelerated rate. Rpl22-deficient mice also display enhanced hematopoietic stem cell (HSC) self-renewal and obstructed differentiation potential, which arises not from reduced protein synthesis but from increased expression of the Rpl22 target, ALOX12, an upstream regulator of fatty acid oxidation (FAO). The increased FAO mediated by Rpl22-deficiency also persists in leukemia cells and promotes their survival. Altogether, these findings reveal that Rpl22 insufficiency enhances the leukemia potential of HSC via non-canonical de-repression of its target, ALOX12, which enhances FAO, a process that may serve as a therapeutic vulnerability of Rpl22 low MDS and AML leukemia cells. Highlights: RPL22 insufficiency is observed in MDS/AML and is associated with reduced survivalRpl22-deficiency produces an MDS-like syndrome and facilitates leukemogenesisRpl22-deficiency does not impair global protein synthesis by HSCRpl22 controls leukemia cell survival by non-canonical regulation of lipid oxidation eTOC: Rpl22 controls the function and transformation potential of hematopoietic stem cells through effects on ALOX12 expression, a regulator of fatty acid oxidation.

A Cross-sectional Cohort Study to Assess Long-term Neurocognitive and Psychiatric Symptoms of Mefloquine Use in Veterans.

INTRODUCTION: To evaluate the associations between neurocognitive and psychiatric health outcomes with mefloquine or any antimalarial exposure. MATERIALS AND METHODS: Medical records were systematically reviewed to identify veterans that indicated antimalarial medication use. Linear regression was performed to examine associations between mefloquine/antimalarial exposure and health outcomes. The mefloquine-exposed group was further compared with normative populations for the same health outcomes. RESULTS: In the adjusted models, no significant differences were noted between the two exposure groups and the unexposed group for any of the health measures (P-value > 0.05). When compared to normative population samples, the mefloquine-exposed group had poorer health and greater neurobehavioral symptom severity or cognitive complaints. CONCLUSION: This study suggests that mefloquine use by veterans referred for intensive evaluation of their military deployment exposures and health was not associated with increased, long-term, neurocognitive/psychiatric symptoms compared to unexposed veterans.

Evaluation of Gender Disparity in Tactical Combat Casualty Care.

INTRODUCTION: Women comprise nearly 19% of the U.S. military and now serve in almost all operational roles, increasing their risk of combat trauma and injuries.3 Data from the Joint Trauma Registry during Operation Enduring Freedom shows that battle-injured females had a higher case fatality rate at 36% compared to their male counterparts at 17%.1 The Tactical Combat Casualty Care curriculum is used to prepare battlefield medics to provide immediate care to wounded service members, but fails to address differences in the care of female versus male casualties. The students, who are presented with life-threatening injuries in simulated trauma scenarios, may be slower to assess, identify, and treat injuries in female patients as compared with male patients. MATERIALS AND METHODS: This observational program analysis was reviewed by the Uniformed Services University Human Research Protections Program and approved for execution as an exempt protocol under the provision of 32 CFR 219.104(d)(1). The study assessed the performance of male and female Mexican military personnel during a Tactical Combat Casualty Care course, using standardized trauma scenarios. Anatomically, correct male and female manikins were used to compare response time for different gender patients presenting with the same injuries. RESULTS: There was a statistically significant increase in time required to complete an initial blood sweep, identify a gunshot wound to the chest, and call for medical evacuation when treating a female patient compared to a male patient. CONCLUSIONS: A lack of female representation in trauma training may have contributed to the higher case fatality rate of female soldiers compared to male soldiers during Operation Enduring Freedom. Female live actors and Gender Retrofit Kits can augment trauma casualty assessment and treatment training scenarios and better prepare our forces to respond to life-threatening emergencies.

Open Chest Duration Following Congenital Cardiac Surgery Increases Risk for Surgical Site Infection.

Surgical site infections (SSI) following congenital heart surgery (CHS) remain a significant source of morbidity. Delayed sternal closure (DSC) is often required to minimize the potential for hemodynamic instability. The purpose of this study was to determine the incidence of SSI among patients undergoing DSC versus primary chest closure (PCC) and to define a potential inflection point for increased risk of SSI as a function of open chest duration (OCD).A retrospective review of our institutional Society of Thoracic Surgeons dataset is to identify patients undergoing CHS at our institution between 2015 and 2020. Incidences of SSI were compared between DSC and PCC patients. DSC patients were evaluated to determine the association of OCD and the incidence of SSI.2582 operations were performed at our institution between 2015 and 2020, including 195 DSC and 2387 PCC cases. The incidence of SSI within the cohort was 1.8% (47/2,582). DSC patients had significantly higher incidences of SSI (17/195, 8.7%) than PCC patients (30/2387, 1.3%, p < 0.001). Further, patients with an OCD of four or more days had a significantly higher incidence of SSI (11/62, 17.7%, p = 0.006) than patients with an OCD less than 4 days (6/115, 5.3%).The incidence of SSI following CHS is higher in DSC patients compared to PCC patients. Prolonged OCD of 4 days or more significantly increases the risk of SSI and represents a potentially modifiable risk factor for SSI predisposition. These data support dedicated, daily post-operative assessment of candidacy for chest closure to minimize the risk of SSI.

Dietary Supplements for Weight Loss: Legal Basis for Excise Tax and Other Government Action to Protect Consumers from a Public Health Menace.

PURPOSE: Dietary supplements sold for weight loss pose a risk to public health due to deceptive claims and unscrupulous manufacturing practices in the context of weak federal regulation. Efforts to strengthen U.S. federal oversight have not been successful, thus action at the state and local levels should be explored. This study investigates proposed action to impose excise taxes on weight-loss supplements. METHODS: We reviewed U.S. federal law on taxation at federal, state, and local levels and precedent for taxation of harmful consumer products to promote public health. We assessed the rationale, legal viability, and potential effectiveness of proposed excise taxes on weight loss supplements. RESULTS: Taxation of tobacco and sweetened beverages is effective in reducing consumer use. Imposition of excise taxes on weight-loss supplements is within the authority of federal, state, and local governments, though is least politically feasible at the federal level. State or local taxation of these products has clear rationale, legal viability, and likelihood of effectiveness in reducing the public health burden posed by these products. CONCLUSIONS: Excise taxation is an effective policy intervention to reduce consumer use, particularly among youth, and is a promising public health strategy to decrease consumer exposure to noxious weight-loss supplements.

BME Career Exploration: Examining Students' Connection with the Field.

A common perception of biomedical engineering (BME) undergraduates is that they struggle to find industry jobs upon graduation. While some statistics support this concern, students continue to pursue and persist through BME degrees. This persistence may relate to graduates' other career interests, though limited research examines where BME students go and why. Scholars are also pushing for research that examines engineering careers in a broader context, beyond traditional industry positions. This study adds to that conversation by asking: How do BME students describe their career interests and perceived job prospects in relation to why they pursue a BME degree? A qualitative study of BME students was performed at a public, R1 institution using semi-structured interviews at three timepoints across an academic year. An open coding data analysis approach explored careerperceptions of students nearing completion of a BME undergraduate degree. Findings indicated that students pursued a BME degree for reasons beyond BME career aspirations, most interestingly as a means to complete an engineering degree that they felt would have interesting enough content to keep them engaged. Participants also discussed the unique career-relevant skills they developed as a BME student, and the career-placement tradeoffs they associated with getting a BME undergraduate degree. Based on these results, we propose research that explores how students move through a BME degree into a career and how career-relevant competencies are communicated in job searches. Additionally, we suggest strategies for BME departments to consider for supporting students through the degree into a career.

Effects of forelimb instrumentation on lameness detection in horses using a portable inertial sensor-based system.

OBJECTIVE: To investigate the effects of a small sensor attached to the pastern region of a forelimb on lameness detection and quantification with a portable inertial sensor-based system (PISBS) for lameness detection and quantification in horses. ANIMALS: 20 adult horses (body weight, 410 to 650 kg) with no visible lameness at the walk. PROCEDURES: In a crossover study design, horses were evaluated at the trot twice using the PISBS with the gyroscope alternately attached to the right forelimb pastern region (as recommended by the manufacturer) or to the left forelimb pastern region (with the sensor flipped 180° on the frontal plane relative to the standard position). Agreement between the 2 instrumentation approaches was investigated graphically and by repeated-measures ANOVA, Pearson correlation analysis, and Bland-Altman analysis. RESULTS: No effects of instrumentation of a forelimb with the gyroscope were detected on the lame limb or limbs or on lameness severity. Attachment of the gyroscope to a forelimb had no effect on forelimb or hind limb lameness (ie, did not cause or mask lameness) as measured with the PISBS. CONCLUSIONS AND CLINICAL RELEVANCE: Instrumentation of a forelimb with a lightweight gyroscope for lameness evaluations with a PISBS had no effects on lameness measurements in horses. Results suggested that, when indicated, the gyroscope can be attached (while flipped 180° on the frontal plane relative to the standard position) to the left forelimb (rather than the right forelimb).

Supratherapeutic Posaconazole Concentration in a Pediatric Transplant Patient With Confirmed Rhizopus Infection.

There are a limited number of studies that guide dosing of posaconazole delayed-release (DR) tablets for the pediatric population. Current FDA-approved doses are only recommended for patients 13 years and older. For younger patients, providers are faced with the challenge of recommending posaconazole doses extrapolated from adult studies or choosing an alternative agent. We report on a case of a 10-year-old patient who experienced a supratherapeutic trough serum concentration and transaminitis after receiving the extrapolated adult dosage of posaconazole DR tablets (300 mg twice daily for the first day, followed by 300 mg daily) for 7 days. In the end, the patient required a smaller dose of 200 mg daily to achieve the desired trough target concentration for the treatment of a Rhizopus neck infection. Our findings highlight the need for additional studies to determine the optimal dosing of posaconazole DR tablets for children.

The Ubiquitin Sensor and Adaptor Protein p62 Mediates Signal Transduction of a Viral Oncogenic Pathway.

The Epstein-Barr virus (EBV) protein LMP1 serves as a paradigm that engages complicated ubiquitination-mediated mechanisms to activate multiple transcription factors. p62 is a ubiquitin sensor and a signal-transducing adaptor that has multiple functions in diverse contexts. However, the interaction between p62 and oncogenic viruses is poorly understood. We recently reported a crucial role for p62 in oncovirus-mediated oxidative stress by acting as a selective autophagy receptor. In this following pursuit, we further discovered that p62 is upregulated in EBV type 3 compared to type 1 latency, with a significant contribution from NF-κB and AP1 activities downstream of LMP1 signaling. In turn, p62 participates in LMP1 signal transduction through its interaction with TRAF6, promoting TRAF6 ubiquitination and activation. As expected, short hairpin RNA (shRNA)-mediated knockdown (KD) of p62 transcripts reduces LMP1-TRAF6 interaction and TRAF6 ubiquitination, as well as p65 nuclear translocation, which was assessed by Amnis imaging flow cytometry. Strikingly, LMP1-stimulated NF-κB, AP1, and Akt activities are all markedly reduced in p62-/- mouse embryo fibroblasts (MEFs) and in EBV-negative Burkitt's lymphoma (BL) cell lines with CRISPR-mediated knockout (KO) of the p62-encoding gene. However, EBV-positive BL cell lines (type 3 latency) with CRISPR-mediated KO of the p62-encoding gene failed to survive. In consequence, shRNA-mediated p62 KD impairs the ability of LMP1 to regulate its target gene expression, promotes etoposide-induced apoptosis, and reduces the proliferation of lymphoblastic cell lines (LCLs). These important findings have revealed a previously unrecognized novel role for p62 in EBV latency and oncogenesis, which advances our understanding of the mechanism underlying virus-mediated oncogenesis. IMPORTANCE As a ubiquitin sensor and a signal-transducing adaptor, p62 is crucial for NF-κB activation, which involves the ubiquitin machinery, in diverse contexts. However, whether p62 is required for EBV LMP1 activation of NF-κB is an open question. In this study, we provide evidence that p62 is upregulated in EBV type 3 latency and, in turn, p62 mediates LMP1 signal transduction to NF-κB, AP1, and Akt by promoting TRAF6 ubiquitination and activation. In consequence, p62 deficiency negatively regulates LMP1-mediated gene expression, promotes etoposide-induced apoptosis, and reduces the proliferation of LCLs. These important findings identified p62 as a novel signaling component of the key viral oncogenic signaling pathway.

Examining the effects of perceived pregnancy discrimination on mother and baby health.

Over the last decade, more than 50,000 pregnancy discrimination claims were filed in the United States (United States Equal Employment Opportunity Commission [U.S. EEOC], 2018a). While pregnancy discrimination claims remain prevalent, research examining the effects of pregnancy discrimination on the well-being and health of working mothers and their babies is lacking. As such, we aim to examine the role of perceived pregnancy discrimination in the workplace on health outcomes for mothers and their babies via mother's stress. We draw on the occupational stress literature and medical research to propose that perceived pregnancy discrimination indirectly relates to mother and baby health via the mother's perceived stress. In our first study, we examine the effects of perceived pregnancy discrimination on mothers' postpartum depressive symptoms via perceived stress. In our second study, we replicate and extend our first study and examine the effects of perceived pregnancy discrimination on mothers' postpartum depressive symptoms and babies' gestational age, Apgar scores, birth weight, and number of doctors' visits, through the mechanism of perceived stress. We find that perceived pregnancy discrimination indirectly relates to increased levels of postpartum depressive symptoms for the mothers, and lower birth weights, lower gestational ages, and increased number of doctors' visits for the babies, via perceived stress of the mothers during pregnancy. Implications for theory and practice, limitations, and future research are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Prototyping for context: exploring stakeholder feedback based on prototype type, stakeholder group and question type.

Engineering designers frequently use prototypes to gather input from stakeholders. Design guidelines recommend the use of quick and simple prototypes early and often in a design process. However, the type and quality of a prototype can influence how stakeholders perceive a new design concept and can therefore impact their responses. Additionally, different levels of experience, expertise, and preparedness for providing input to designers may lead stakeholders from different geographical or cultural settings to provide different responses, making the format of a prototype even more influential. Although design practitioners are known to intentionally align their prototyping approach with the specific design question to be answered, it is unclear the extent to which prototyping approaches should vary based on the stakeholders, context, and setting of a design project. To investigate how the format and quality of prototypes influence stakeholders' responses, we conducted a field study with various medical professionals in Ghana. We presented prototypes for a medical device in different formats to stakeholders and collected responses to the design through semi-structured interviews. We found that professional expertise, prototype format, and question type influenced the types of responses that stakeholders provided. These findings suggest that designers seeking input from stakeholders on new concepts should consider context-specific prototyping strategies, especially when designing at distance and across cultures.

Validation of the Omni: A Novel, Multimodality, and Longitudinal Surgical Skills Assessment.

OBJECTIVE: The breadth of technical skills included in general surgery training continues to expand. The current competency-based training model requires assessment tools to measure acquisition, learning, and mastery of technical skill longitudinally in a reliable and valid manner. This study describes a novel skills assessment tool, the Omni, which evaluates performance in a broad range of skills over time. DESIGN: The 5 Omni tasks, consisting of open bowel anastomosis, knot tying, laparoscopic clover pattern cut, robotic needle drive, and endoscopic bubble pop, were developed by general surgery faculty. Component performance metrics assessed speed, accuracy, and quality, which were scaled into an overall score ranging from 0 to 10 for each task. For each task, ANOVAs with Scheffé's post hoc comparisons and Pearson's chi-squared tests compared performance between 6 resident cohorts (clinical years (CY1-5) and research fellows (RF)). Paired samples t-tests evaluated changes in performance across academic years. Cronbach's alpha coefficient determined the internal consistency of the Omni as an overall assessment. SETTING: The Omni was developed by the Department of Surgery at Duke University. Annual assessment and this research study took place in the Surgical Education and Activities Lab. PARTICIPANTS: All active general surgery residents in 2 consecutive academic years spanning 2015 to 2017. RESULTS: A total of 62 general surgery residents completed the Omni and 39 (67.2%) of those residents completed the assessment in 2 consecutive years. Based on data from all residents' first assessment, statistically significant differences (p < 0.05) were observed among CY cohorts for bowel anastomosis, robotic, and laparoscopic task metrics. By pair-wise comparisons, mean bowel anastomosis scores distinguished CY1 from CY3-5 and CY2 from CY5. Mean robotic scores distinguished CY1 from RF, and mean laparoscopic scores distinguished CY1 from RF, CY3, and CY5 in addition to CY2 from CY3. Mean scores in performance on the knot tying and endoscopic tasks were not significantly different. Statistically significant improvement in mean scores was observed for all tasks from year 1 to year 2 (all p < 0.02). The internal consistency analysis revealed an alpha coefficient of 0.656. CONCLUSIONS: The Omni is a novel composite assessment tool for surgical technical skill that utilizes objective measures and scoring algorithms to evaluate performance. In this pilot study, 3 tasks demonstrated discriminative ability of performance by CY, and all 5 tasks demonstrated construct validity by showing longitudinal improvement in performance. Additionally, the Omni has adequate internal consistency for a formative assessment. These results suggest the Omni holds promise for the evaluation of resident technical skill and early identification of outliers requiring intervention.

Using design strategies from microfluidic device patents to support idea generation.

Microfluidics has been an important method in providing answers to a wide variety of research questions in chemistry, biochemistry, and biology. Microfluidic designers benefit from instructional textbooks describing foundational principles and practices in developing microfluidic devices; however, these texts do not offer guidance about how to generate design concepts for microfluidic devices. Research on design in related fields, such as mechanical engineering, documents the difficulties engineers face when attempting to generate novel ideas. For microfluidic device designers, support during idea generation may lead to greater exploration of potential innovations in design. To investigate successful idea generation in microfluidics, we analyzed successful microfluidic US patents, selecting those with the key word "microfluidic" over a 2-year period. After analyzing the features and functions of 235 patents, we identified 36 distinct design strategies in microfluidic devices. We document each strategy, and demonstrate their usefulness in a concept generation study of practitioners in microfluidic design. While some of the identified design strategies may be familiar to microfluidic designers, exposure to this large set of strategies helped participants generate more diverse, creative, and unique microfluidic design concepts, which are considered best practices in idea generation.

Novice designers' use of prototypes in engineering design.

Prototypes are essential tools in product design processes, but are often underutilized by novice designers. To help novice designers use prototypes more effectively, we must first determine how they currently use prototypes. In this paper, we describe how novice designers conceptualized prototypes and reported using them throughout a design project, and compare reported prototyping use to prototyping best practices. We found that some of the reported prototyping practices by novice designers, such as using inexpensive prototypes early and using prototypes to define user requirements, occurred infrequently and lacked intentionality. Participants' initial descriptions of prototypes were less sophisticated than how they later described using them and only upon prompted reflection did participants recognize more specific benefits of using prototypes.

Developing a Checklist: Consensus Via a Modified Delphi Technique.

OBJECTIVE: To create a universal checklist of key preparatory steps to aid anesthesiologists in patient separation from cardiopulmonary bypass. DESIGN: Multistep, iterative survey with statistically guided refinement of survey items using a modified Delphi technique. SETTING: Internet-based surveys. PARTICIPANTS: Ninety active members of the Society of Cardiovascular Anesthesiologists volunteered to participate, including geographically distributed private practice and academic physicians. INTERVENTIONS: A series of checklist items was created and distributed to 90 anesthesiologists, who assessed each item's importance in preparing for patient separation from cardiopulmonary bypass and added, deleted, or modified any items as they saw fit. Items meeting a threshold of greater than 90% group acceptance were carried forward to a second survey. These items then were evaluated using a 5-point Likert scale to grade relative importance and then compared with the group's responses, creating a third survey with refined checklist items. The results then were used to generate a final survey based on each item achieving certain predefined statistical criteria, which then were scored again by the participants, generating a final checklist via statistically guided consensus. MEASUREMENTS AND MAIN RESULTS: An initial checklist containing 28 possible items was proposed to the participants. After the iterative process was completed, a final checklist of 10 items deemed essential to prepare for bypass separation was created. CONCLUSIONS: A checklist to aid in bypass separation was created with key steps derived from a statistically driven Delphi process. This technique of iterative consensus building may be useful in developing additional safety checklists.

Vascular Targeted Radioimmunotherapy for the Treatment of Glioblastoma.

Glioblastoma is characterized by an aggressive and aberrant vascular network that promotes tumor progression and hinders effective treatment; the median survival is 16 mo despite standard-of-care therapies. There is a need to improve therapeutic options for this disease. We hypothesized that antibody targeting of the vascular endothelium of glioblastoma with cytotoxic short-range, high-energy α-particles would be an effective therapeutic approach. METHODS: E4G10, an antibody directed at an epitope of monomeric vascular endothelium cadherin that is expressed in tumor neovasculature and on endothelial progenitor cells in the bone marrow, was labeled with α-particle-emitting 225Ac. Pharmacokinetic studies investigated the tissue distribution and blood clearance of the 225Ac-E4G10 radioimmunoconstruct in a transgenic Nestin-tumor virus A (Ntva) mouse model of high-grade glioblastoma. Histologic analysis was used to demonstrate local therapeutic effects in treated brain tumor sections. Radioimmunotherapy with 225Ac-E4G10 was performed in Ntva mice to assess overall survival alone and in combination with temozolomide, the standard-of-care chemotherapeutic agent. RESULTS: 225Ac-E4G10 was found to accumulate in tissues expressing the target antigen. Antivascular α-particle therapy of glioblastoma in the transgenic Ntva model resulted in significantly improved survival compared with controls and potent control of tumor growth. Adding the chemotherapeutic temozolomide to the treatment increased survival to 30 d (vs. 9 d for vehicle-treated animals). Histologic analyses showed a remodeled glioblastoma vascular microenvironment. CONCLUSION: Targeted α-particle antivascular therapy is shown for the first time to be effective in increasing overall survival in a solid tumor in a clinically relevant transgenic glioblastoma mouse model.

Saddle-Shaped Annuloplasty Improves Leaflet Coaptation in Repair for Ischemic Mitral Regurgitation.

BACKGROUND: Current repair results for ischemic mitral regurgitation (IMR) with undersized annuloplasty rings are characterized by high IMR recurrence rates. Current annuloplasty rings treat annular dilatation, but they do little to improve (and may actually exacerbate) leaflet tethering. New saddle-shaped annuloplasty rings have been shown to maintain or restore a more physiologic annular and leaflet geometry and function. Using a porcine IMR model, we sought to demonstrate the influence of annuloplasty ring shape on leaflet coaptation. METHODS: Eight weeks after posterolateral infarct, eight pigs with grade 2+ or higher IMR were randomized to undergo either a 28-mm flat ring annuloplasty (n = 4) or a 28-mm saddle-shaped ring annuloplasty (n = 4). Real-time three-dimensional echocardiography and a customized image analysis protocol allowed three-dimensional assessment of leaflet coaptation before and after annuloplasty. RESULTS: Total leaflet coaptation area was significantly higher after saddle-shaped ring annuloplasty (109.6 ± 26.9 mm(2)) compared with flat ring annuloplasty (46.2 ± 7.7 mm(2), p <0.01). After annuloplasty, total coaptation area decreased by 87.5 mm(2) (or 65%) in the flat annuloplasty group (p = 0.01), whereas total coaptation area increased by 22.2 mm(2) (or 25%) in the saddle-shaped annuloplasty group (p = 0.28). CONCLUSIONS: This study shows that the use of undersized saddle-shaped annuloplasty rings in mitral valve repair for IMR improves leaflet coaptation, whereas the use of undersized flat annuloplasty rings worsens leaflet coaptation. Because one of Carpentier's fundamental principles of mitral valve repair (durability) is to create a large surface of coaptation, saddle-shaped annuloplasty may increase repair durability.

Human cytomegalovirus modulates monocyte-mediated innate immune responses during short-term experimental latency in vitro.

UNLABELLED: The ability of human cytomegalovirus (HCMV) to establish lifelong persistence and reactivate from latency is critical to its success as a pathogen. Here we describe a short-term in vitro model representing the events surrounding HCMV latency and reactivation in circulating peripheral blood monocytes that was developed in order to study the immunological consequence of latent virus carriage. Infection of human CD14(+) monocytes by HCMV resulted in the immediate establishment of latency, as evidenced by the absence of particular lytic gene expression, the transcription of latency-associated mRNAs, and the maintenance of viral genomes. Latent HCMV induced cellular differentiation to a macrophage lineage, causing production of selective proinflammatory cytokines and myeloid-cell chemoattractants that most likely play a role in virus dissemination in the host. Analysis of global cellular gene expression revealed activation of innate immune responses and the modulation of protein and lipid synthesis to accommodate latent HCMV infection. Remarkably, monocytes harboring latent virus exhibited selective responses to secondary stimuli known to induce an antiviral state. Furthermore, when challenged with type I and II interferon, latently infected cells demonstrated a blockade of signaling at the level of STAT1 phosphorylation. The data demonstrate that HCMV reprograms specific cellular pathways in monocytes, most notably innate immune responses, which may play a role in the establishment of, maintenance of, and reactivation from latency. The modulation of innate immune responses is likely a viral evasion strategy contributing to viral dissemination and pathogenesis in the host. IMPORTANCE: HCMV has the ability to establish a lifelong infection within the host, a phenomenon termed latency. We have established a short-term model system in human peripheral blood monocytes to study the immunological relevance of latent virus carriage. Infection of CD14(+) monocytes by HCMV results in the generation of latency-specific transcripts, maintenance of viral genomes, and the capacity to reenter the lytic cycle. During short-term latency in monocytes the virus initiates a program of differentiation to inflammatory macrophages that coincides with the modulation of cytokine secretion and specific cellular processes. HCMV-infected monocytes are hindered in their capacity to exert normal immunoprotective mechanisms. Additionally, latent virus disrupts type I and II interferon signaling at the level of STAT1 phosphorylation. This in vitro model system can significantly contribute to our understanding of the molecular and inflammatory factors that initiate HCMV reactivation in the host and allow the development of strategies to eradicate virus persistence.

Impact of wall thickness and saccular geometry on the computational wall stress of descending thoracic aortic aneurysms.

BACKGROUND: Wall stress calculated using finite element analysis has been used to predict rupture risk of aortic aneurysms. Prior models often assume uniform aortic wall thickness and fusiform geometry. We examined the effects of including local wall thickness, intraluminal thrombus, calcifications, and saccular geometry on peak wall stress (PWS) in finite element analysis of descending thoracic aortic aneurysms. METHODS AND RESULTS: Computed tomographic angiography of descending thoracic aortic aneurysms (n=10 total, 5 fusiform and 5 saccular) underwent 3-dimensional reconstruction with custom algorithms. For each aneurysm, an initial model was constructed with uniform wall thickness. Experimental models explored the addition of variable wall thickness, calcifications, and intraluminal thrombus. Each model was loaded with 120 mm Hg pressure, and von Mises PWS was computed. The mean PWS of uniform wall thickness models was 410 ± 111 kPa. The imposition of variable wall thickness increased PWS (481 ± 126 kPa, P<0.001). Although the addition of calcifications was not statistically significant (506 ± 126 kPa, P=0.07), the addition of intraluminal thrombus to variable wall thickness (359 ± 86 kPa, P ≤ 0.001) reduced PWS. A final model incorporating all features also reduced PWS (368 ± 88 kPa, P<0.001). Saccular geometry did not increase diameter-normalized stress in the final model (77 ± 7 versus 67 ± 12 kPa/cm, P=0.22). CONCLUSIONS: Incorporation of local wall thickness can significantly increase PWS in finite element analysis models of thoracic aortic aneurysms. Incorporating variable wall thickness, intraluminal thrombus, and calcifications significantly impacts computed PWS of thoracic aneurysms; sophisticated models may, therefore, be more accurate in assessing rupture risk. Saccular aneurysms did not demonstrate a significantly higher normalized PWS than fusiform aneurysms.