Structure of phosphorylated-like RssB, the adaptor delivering σs to the ClpXP proteolytic machinery, reveals an interface switch for activation.

In enterobacteria such as Escherichia coli, the general stress response is mediated by σs, the stationary phase dissociable promoter specificity subunit of RNA polymerase. σs is degraded by ClpXP during active growth in a process dependent on the RssB adaptor, which is thought to be stimulated by the phosphorylation of a conserved aspartate in its N-terminal receiver domain. Here we present the crystal structure of full-length RssB bound to a beryllofluoride phosphomimic. Compared to the structure of RssB bound to the IraD anti-adaptor, our new RssB structure with bound beryllofluoride reveals conformational differences and coil-to-helix transitions in the C-terminal region of the RssB receiver domain and in the interdomain segmented helical linker. These are accompanied by masking of the α4-ß5-α5 (4-5-5) "signaling" face of the RssB receiver domain by its C-terminal domain. Critically, using hydrogen-deuterium exchange mass spectrometry, we identify σs-binding determinants on the 4-5-5 face, implying that this surface needs to be unmasked to effect an interdomain interface switch and enable full σs engagement and hand-off to ClpXP. In activated receiver domains, the 4-5-5 face is often the locus of intermolecular interactions, but its masking by intramolecular contacts upon phosphorylation is unusual, emphasizing that RssB is a response regulator that undergoes atypical regulation.

Twenty-five years of observations from the International Registry of Acute Aortic Dissection (IRAD) and its impact on the cardiovascular scientific community.

OBJECTIVE: The International Registry of Acute Aortic Dissection (IRAD) celebrated its 25th anniversary in January 2021. This study evaluated IRAD's role in promoting the understanding and management of acute aortic dissection (AD) over these years. METHODS: IRAD studies were identified, analyzed, and ranked according to their citations per year (c/y) to determine the most-cited IRAD studies and topics. A systematic search of the literature identified cardiovascular guidelines on the diagnosis and management of acute AD. Consequently, IRAD's presence and impact were quantified using these documents. RESULTS: Ninety-seven IRAD studies were identified, of which 82 obtained more than 10 cumulative citations. The median c/y index was 7.33 (25th-75th percentile, 4.01-16.65). Forty-two studies had a greater than median c/y index and were considered most impactful. Of these studies, most investigated both type A and type B AD (n = 17, 40.5%) and short-term outcomes (n = 26, 61.9%). Nineteen guideline documents were identified from 26 cardiovascular societies located in Northern America, Europe, and Japan. Sixty-nine IRAD studies were cited by these guidelines, including 38 of the 42 most-impactful IRAD studies. Among them, partial thrombosis of the false lumen as a predictor of postdischarge mortality and aortic diameters as a predictor of type A occurrence were determined as most-impactful specific IRAD topics by their c/y index. CONCLUSIONS: IRAD has had and continues to have an important role in providing observations, credible knowledge, and research questions to improve the outcomes of patients with acute AD.

Age, sex, and contemporary outcomes in surgical repair of type A aortic dissection: Insights from the National Inpatient Sample.

Objective: Acute type A aortic dissection (ATAAD) is a surgical emergency with significant morbidity and mortality, as well as significant center-level variation in outcomes. Our study aims to leverage a nationally representative database to assess contemporary in-hospital outcomes in surgical repair of ATAAD, as well as the association of age and sex with outcomes. Methods: The National Inpatient Sample was queried to identify hospital discharge records of patients aged ≥18 years who underwent urgent surgical repair of ATAAD between 2017 and 2018. Patients with a diagnosis of thoracic aortic dissection, who underwent surgical intervention of the ascending aorta, were identified. Patient demographics were assessed, and predictors of in-hospital mortality were identified. Results: We identified 7805 weighted cases of surgically repaired ATAAD nationally, with an overall mortality of 15.3%. Mean age was 60.0 ± 13.6 years. There was a male predominance, although female subjects made up a larger proportion of older age groups-female subjects up 18.4% of patients younger than 40 years with ATAAD but 53.6% of patients older than 80 years. In multivariable analysis controlling for sex, race, comorbidities, and malperfusion, age was a significant predictor of mortality. Patients aged 71 to 80 years had a 5.3-fold increased risk of mortality compared with patients ≤40 years old (P < .001), and patients aged >80 years had a 6.8-fold increased risk of mortality (P < .001). Sex was not significantly associated with mortality. Conclusions: Surgical repair of ATAAD continues to carry high risk of morbidity and mortality, with outcomes impacted significantly by patient age, regardless of patient comorbidity burden.

Surgical and endovascular repair for type B aortic dissections with mesenteric malperfusion syndrome: A systematic review of in-hospital mortality.

Objectives: Mesenteric malperfusion is a feared complication of aortic dissection, with high mortality. The purpose of this study was to systematically review in-hospital mortality (IHM) of endovascular and surgical management of acute and chronic Stanford type B aortic dissections (TBAD) complicated by mesenteric malperfusion (MesMP). Methods: A systematic search of English language articles was conducted in relevant databases. Data on patient demographics, procedure details, and survival outcomes were collected. Reports were classified by type of intervention performed. Studies that failed to report patient-level outcomes based on specific intervention performed or IHM were excluded. Retrospective chart review of previously published data from a single institution was also performed to further identify cases of TBAD that were managed endovascularly. The Fisher exact test was performed to determine statistical significance. Results: In total, 37 articles were suitable for inclusion in this systematic review, which yielded 149 patients with a median age 55.0 years (interquartile range, 46.5-65 years) and 79% being male. Overall, in-hospital mortality was 12.8% (19/149) and was similar between endovascular and open surgical interventions (13% vs 11%, P = .99). Among endovascular strategies, IHM was greater, although not statistically significant in the thoracic endovascular aortic repair group compared with the fenestration/stenting without thoracic endovascular aortic repair group (24% vs 11%, P = .15). Conclusions: Multiple strategies exist for the management of TBAD with MesMP; however, a majority of cases were managed endovascularly. Despite advances in therapies, mortality remains high at 13%.

Outcomes of acute type A aortic dissection operations performed by early-career cardiovascular surgeons.

Objective: Surgical outcomes of acute type A aortic dissection have been recognized to be associated with the surgical volume of individual hospitals and surgeons. In this study, we aimed to investigate the results and learning curves of acute type A aortic dissection operations performed by early-career cardiovascular surgeons. Methods: A total of 248 surgical repairs of acute type A aortic dissections were conducted at a tertiary medical center between 2010 and 2018. By using the cumulative sum test, cardiovascular surgeons in their early career were identified, and their performances were assessed. The outcomes of patients who were operated by early-career cardiovascular surgeons were compared with those by experienced or senior surgeons. Results: During the study period, 202 (81.5%) of the 248 acute type A aortic dissection operations were performed primarily by the 4 newly appointed attending cardiovascular surgeons. In cumulative sum curves, all surgeons exhibited a steady performance throughout the study period. On the basis of our institutional result of acute type A aortic dissection operation, early career was defined as performing fewer than 32 acute type A aortic dissection operations. The 30-day mortality rates of acute type A aortic dissection operations performed by early-career surgeons were equivalent to those performed by experienced/senior surgeons (10.9% vs 12.5%, P = .844). There was also no difference in mid-term overall survival and aortic event-free survival between the 2 groups (P = .638 and P = .574, respectively). Conclusions: In a center with a well-established program, cardiovascular surgeons could accomplish surgical repair of acute type A aortic dissection with adequate early- and mid-term results from the initiation of their careers.

Outcomes of acute type A aortic dissection repair: Daytime versus nighttime.

Objective: We sought to report our experience of repairing acute type A aortic dissection (ATAAD) over 21 years during in-hours versus out-of-hours before and after the establishment of specialized aortic service and rota. Methods: A retrospective analysis of all patients who had ATAAD repair between November 1998 and December 2019 in our center. In-hours were defined as 08:00 to 19:59 hours and out of hours were defined as 20:00 to 07:59 hours. Results: A total of 286 patients underwent repair of ATAAD. Eighty operations took place during the prerota period (43 operations in hours, 37 out of hours) and 206 operations during the specialized rota period (110 in hours, 96 out of hours). There was no difference in 30-day mortality between the in-hours and out-of-hours groups in either the prerota (23.3% vs 32.4%; P = .36) or specialized rota periods (11.6% vs 11.5%; P = .94). Mean number of cases per year increased by 83% between the prerota and specialized rota periods. Thirty-day mortality reduced in both the in-hours (23.3% vs 11.6%) and out-of-hours (32.4% vs 11.5%) groups since introduction of the specialized aortic rota. Conclusions: Outcomes in repair of ATAAD during in-hours and out-of-hours periods are similar when operated on in a specialized unit with a dedicated aortic team. This emphasizes the current global trend of service centralization without particular attention to time of day to operate on such critical cohort patients.

To Tweet or Not to Tweet? A Look at Radiology Societies' Use of Twitter.

INTRODUCTION: Twitter is the most used social media platform by medical professionals and has become an effective way to disseminate ideas and information. AIM: To evaluate Twitter usage by some of the larger diagnostic radiology (DR) and interventional radiology (IR) societies. MATERIALS AND METHODS: Data were collected from the publicly available Twitter analytics platform, Twitonomy™. Data collected included the number of followers, Twitter output, user engagement and changes of these parameters between January 2017 and January 2019. RESULTS: DR societies have the largest number of followers. The IR group increased its number of followers by 5139 (55%) compared with 10013 (18%) by the DR group during the period studied. In both years, the IR group posted more tweets/day compared with the DR group (6.6 vs. 4.7). Although user engagement increased for both IR and DR societies, the IR subgroup had a highly engaged user audience with a similar number of 'likes' to the DR group despite their larger Twitter following (DR 65500 vs. IR 14411 in 2019). CONCLUSIONS: The IR societies studied experienced comparable Twitter engagement to the larger DR societies. The societies with the smallest number of followers (BSIR and CIRSE) enjoyed the largest relative increase in followers over the study period. IR societies should be encouraged by these results to continue to publicize their work on social media and increase awareness of the specialty.

Successful Conservative Treatment of a Type A Aortic Intramural Hematoma.

Type A intramural hematoma (IMH) constitutes a variant of acute aortic syndrome. Western guidelines support an aggressive surgical approach, whereas Asian centers propose initial conservative treatment. Further expanding on this notion, we present a case of conservative subacute type A IMH management, resulting in radical hematoma resorption within 4 weeks. (Level of Difficulty: Beginner.).

Resonance assignments of N-terminal receiver domain of sigma factor S regulator RssB from Escherichia coli.

Sigma factor S (σS) are master regulator responsible for the survival of bacteria under extreme conditions. Bacteria start specific gene expression via σS promoter recognition, activating various responses to cope with external conditions. Although this self-protection mechanism is vital for bacteria to propagate and evolve, there are many puzzling research questions to be answered. For example, while interactions between σS, transcription regulator RssB, and anti-adaptor Ira proteins are believed to be responsible for controlling the cellular level of σS, their competition mechanism among them remains elusive. Furthermore, there are still debates on the location of the interface of Ira proteins and RssB and whether phosphorylation on the receiver domain is essential for σS activation remains elusive. While there is one crystal structure for the Escherichia coli receiver domain deposited in the database, the missing regions in the structure become an obstacle for functional and interactive studies. Despite attempts, there is no structure for any protein complex in this important biological process, making it one overlooked area in bacterial transcription. Here, using solution-state NMR, our near-complete resonance assignment for the receiver domain of E. coli RssB provides a basis for future structure determination and interaction studies with its many known and putative ligands.

Malperfusion syndromes in type A aortic dissection: what we have learned from IRAD.

Patients presenting with type A acute aortic dissection (TAAD) complicated by malperfusion syndromes represent one of the highest surgical risk cohorts for cardiovascular surgeons. In the setting of aortic dissection, end-organ ischemia may involve any of the major arterial side branches resulting in myocardial, cerebral, spinal cord, visceral and/or limb ischemia. In TAAD patients with malperfusion, notwithstanding continuous improvement in diagnostic and management strategies, surgical and clinical outcomes remain poor and the optimal therapy is controversial. The present review aimed to assess current evidence on TAAD patients with the complication of malperfusion, as enunciated by the International Registry of Acute Aortic Dissection (IRAD) investigators.

#TwittIR: Understanding and Establishing a Twitter Ecosystem for Interventional Radiologists and Their Practices.

The use of social media among interventional radiologists is increasing, with Twitter receiving the most attention. Twitter is an ideal forum for open exchange of ideas from around the world. However, it is important for Twitter users to gain a rudimentary understanding of the many potential communication pathways to connect with other users. An intentional approach to Twitter is vital to efficient and successful use. This article describes several common communication pathways that can be utilized by physicians in their interventional radiology practice.

Early Outcomes of Acute Retrograde Dissection From the International Registry of Acute Aortic Dissection.

To provide data on the management and outcomes of patients with acute retrograde aortic dissection (AD) originating from a tear in the descending aorta with extension into the aortic arch or ascending aorta. All patients enrolled in the International Registry of Acute Aortic Dissection from 1996-2015 were reviewed. Retrograde AD was defined by primary tear in the descending aorta with proximal extension into the arch or ascending aorta. Primary end points were in-hospital management strategy and mortality. We identified 101 patients with retrograde AD (67 men; 63.2 ± 14.0 years). During index hospitalization, medical (MED), open surgical (SURG), and endovascular (ENDO) therapies were undertaken in 44, 33, and 22 patients, respectively. The SURG group presented with larger ascending aorta (P = 0.04) and more frequent ascending aortic involvement (81.8% [27/33] vs 22.7% [15/66], P < 0.001) compared with the MED and ENDO groups. Early mortality rate was 9.1% (4/44), 18.2% (6/33), and 13.6% (3/22), for the MED, SURG, and ENDO groups (P = 0.51), respectively. A favorable early mortality rate was observed in patients with retrograde extension limited to the arch (8.6% [5/58]) vs into the ascending aorta (18.6% [8/43], P = 0.14). Early mortality rate of patients with retrograde AD with primary tear in the descending aorta (12.9% [13/101]) was significantly lower than those with classic type A AD presenting with primary tear in the ascending aorta (20.0% [195/977], P = 0.001). A subset of patients with acute retrograde AD originating from primary tear in the descending aorta might be managed less invasively with acceptable early results, particularly among those with proximal extension limited to the arch.

Translational Repression of the RpoS Antiadapter IraD by CsrA Is Mediated via Translational Coupling to a Short Upstream Open Reading Frame.

CsrA is a global regulatory RNA binding protein that has important roles in regulating carbon metabolism, motility, biofilm formation, and numerous other cellular processes. IraD functions as an antiadapter protein that inhibits RssB-mediated degradation of RpoS, the general stress response and stationary-phase sigma factor of Escherichia coli Here we identified a novel mechanism in which CsrA represses iraD translation via translational coupling. Expression studies with quantitative reverse transcriptase PCR, Western blotting, and lacZ fusions demonstrated that CsrA represses iraD expression. Gel mobility shift, footprint, and toeprint studies identified four CsrA binding sites in the iraD leader transcript, all of which are far upstream of the iraD ribosome binding site. Computational modeling and RNA structure mapping identified an RNA structure that sequesters the iraD Shine-Dalgarno (SD) sequence. Three open reading frames (ORFs), all of which are translated, were identified in the iraD leader region. Two of these ORFs do not affect iraD expression. However, the translation initiation region of the third ORF contains three of the CsrA binding sites, one of which overlaps its SD sequence. Furthermore, the ORF stop codon overlaps the iraD start codon, a sequence arrangement indicative of translational coupling. In vivo expression and in vitro translation studies with wild-type and mutant reporter fusions demonstrated that bound CsrA directly represses translation initiation of this ORF. We further established that CsrA-dependent repression of iraD translation occurs entirely via translational coupling with this ORF, leading to accelerated iraD mRNA decay.IMPORTANCE CsrA posttranscriptionally represses gene expression associated with stationary-phase bacterial growth, often in opposition to the transcriptional effects of the stationary-phase sigma factor RpoS. We show that CsrA employs a novel regulatory mechanism to repress translation of iraD, which encodes an antiadapter protein that protects RpoS against proteolysis. CsrA binds to four sites in the iraD leader transcript but does not directly occlude ribosome binding to the iraD SD sequence. Instead, CsrA represses translation of a short open reading frame encoded upstream of iraD, causing repression of iraD translation via translational coupling. This finding offers a novel mechanism of gene regulation by the global regulator CsrA, and since RpoS can activate csrA transcription, this also highlights a new negative-feedback loop within the complex Csr and RpoS circuitry.

IRAD experience on surgical type A acute dissection patients: results and predictors of mortality.

Type A acute aortic dissection (TAAD) is a disease that has a catastrophic impact on a patient's life and emergent surgery represents a key goal of early treatment. Despite continuous improvements in imaging techniques, medical therapy and surgical management, early mortality in patients undergoing TAAD repair still remains high, ranging from 17% to 26%. In this setting, the International Registry of Acute Aortic Dissection (IRAD), the largest worldwide registry for acute aortic dissection, was established to assess clinical characteristics, management and outcomes of TAAD patients. The present review aimed to evaluate and comment on outcomes of TAAD surgery as reported from IRAD series.

Update in the management of type B aortic dissection.

Stanford type B aortic dissection (TBAD) is a life-threatening aortic disease. The initial management goal is to prevent aortic rupture, propagation of the dissection, and symptoms by reducing the heart rate and blood pressure. Uncomplicated TBAD patients require prompt medical management to prevent aortic dilatation or rupture during subsequent follow-up. Complicated TBAD patients require immediate invasive management to prevent death or injury caused by rupture or malperfusion. Recent developments in diagnosis and management have reduced mortality related to TBAD considerably. In particular, the introduction of thoracic stent-grafts has shifted the management from surgical to endovascular repair, contributing to a fourfold increase in early survival in complicated TBAD. Furthermore, endovascular repair is now considered in some uncomplicated TBAD patients in addition to optimal medical therapy. For more challenging aortic dissection patients with involvement of the aortic arch, hybrid approaches, combining open and endovascular repair, have had promising results. Regardless of the chosen management strategy, strict antihypertensive control should be administered to all TBAD patients in addition to close imaging surveillance. Future developments in stent-graft design, medical therapy, surgical and hybrid techniques, imaging, and genetic screening may improve the outcomes of TBAD patients even further. We present a comprehensive review of the recommended management strategy based on current evidence in the literature.

Acute type B aortic dissection: insights from the International Registry of Acute Aortic Dissection.

Acute type B aortic dissection comprises approximately one-third of all aortic dissection cases. Although this catastrophic cardiovascular condition was first described in the medical literature over two centuries ago, data on the optimal diagnostic and treatment modalities for type B dissection was slow to evolve throughout the latter half of the twentieth century, even as newer diagnostic techniques and management strategies became commonplace. To further elucidate contemporary practice patterns and outcomes of aortic dissection, the International Registry of Acute Aortic Dissection (IRAD) was established in 1996. Over the past two decades, IRAD publications have steadily increased our knowledge and understanding about aortic dissection. Specifically in recent years, analyses of IRAD data have gone beyond simply characterizing the patient with acute type B aortic dissection and have attempted to identify the means by which the outcome of such a patient could be improved. Thus, we present herein three areas in which IRAD data has recently advanced our understanding of acute type B aortic dissection: temporal classification especially for the subacute time period, risk stratification for identifying complicated cases, and thoracic endovascular aortic repair (TEVAR).

Performance of ZDOCK in CAPRI rounds 20-26.

We report the performance of our approaches for protein-protein docking and interface analysis in CAPRI rounds 20-26. At the core of our pipeline was the ZDOCK program for rigid-body protein-protein docking. We then reranked the ZDOCK predictions using the ZRANK or IRAD scoring functions, pruned and analyzed energy landscapes using clustering, and analyzed the docking results using our interface prediction approach RCF. When possible, we used biological information from the literature to apply constraints to the search space during or after the ZDOCK runs. For approximately half of the standard docking challenges we made at least one prediction that was acceptable or better. For the scoring challenges we made acceptable or better predictions for all but one target. This indicates that our scoring functions are generally able to select the correct binding mode.

Natural history of thoracic aortic aneurysms: size matters, plus moving beyond size.

Thoracic aortic aneurysms (TAAs) are a prevalent and deadly disease that, without diagnosis and treatment, eventuates in life-threatening aortic dissection or rupture. While TAAs normally grow in an indolent manner, once a certain size (a "hinge point") is reached, the risk of dissection, rupture, and death increases dramatically. By virtue of their common clinical "silence," many TAAs are not diagnosed until such complications occur. While size is a helpful criterion for intervention, there is a need for parameters and markers besides aortic aneurysm size for use in diagnosing and monitoring TAAs so as to prevent natural complications of this disease.

Chronobiology in aortic diseases - "is this really a random phenomenon?".

Although acute aortic rupture or dissection is relatively uncommon, it ranks in third position among necropsy-confirmed causes of out-of-hospital sudden death in the general population. Similar to other acute cardiovascular events (e.g., acute myocardial infarction, sudden death, stroke, and pulmonary embolism) there is a growing body of evidence regarding temporal patterns in onset, characterized by circadian, seasonal and weekly variations for aortic aneurysms. On one hand, it is possible that these cardiovascular diseases share common underlying pathophysiologic mechanisms, e.g., increase in blood pressure, heart rate, sympathetic activity, basal vascular tone, vasoconstrictive hormones, and prothrombotic tendency. On the other hand, the possibility exists that the connecting link is an internal disruption (dyssynchrony) of some molecular mechanisms intrinsic to the peripheral biological clock (that of cardiomyocyte is the most widely investigated). Such disruption may contribute to cardiovascular disease and biological rhythms - an intriguing hypothesis for future research.