Dissecting quantitative trait nucleotides by saturation genome editing.

Genome editing technologies have the potential to transform our understanding of how genetic variation gives rise to complex traits through the systematic engineering and phenotypic characterization of genetic variants. However, there has yet to be a system with sufficient efficiency, fidelity, and throughput to comprehensively identify causal variants at the genome scale. Here we explored the ability of templated CRISPR editing systems to install natural variants genome-wide in budding yeast. We optimized several approaches to enhance homology-directed repair (HDR) with donor DNA templates, including donor recruitment to target sites, single-stranded donor production by bacterial retrons, and in vivo plasmid assembly. We uncovered unique advantages of each system that we integrated into a single superior system named MAGESTIC 3.0. We used MAGESTIC 3.0 to dissect causal variants residing in 112 quantitative trait loci across 32 environmental conditions, revealing an enrichment for missense variants and loci with multiple causal variants. MAGESTIC 3.0 will facilitate the functional analysis of the genome at single-nucleotide resolution and provides a roadmap for improving template-based genome editing systems in other organisms.

FT-IR spectroscopy analysis of HF-treated mineral soils, a direct approach for deciphering organo-mineral interactions.

Soil organic matter (SOM) constitutes roughly 60% organic carbon (OC) and therefore plays a crucial role in regulating global climate. However, our understanding of the long-term dynamics of the soil carbon pool remains constrained by limitations in analytical approaches capable of providing high resolution molecular-level information from arguably the most complex biomaterial on the planet. In this contribution, we combine hydrofluoric acid (HF) treatment with a spectroscopic approach as a strategy to provide refined molecular-level information on the interactions between soil minerals and SOM. Critically, we have not seen the use of this combined approach anywhere in the literature and strongly believe that it could allow us to improve our overall understanding to the mechanisms and pathways that regulate SOM transformation. Results clearly illustrates which organic structures are preferentially adsorbed to soil minerals and are likely to be protected from degradation, as well as spatial co-variations of SOM with specific mineral components such as Al3+, Si4+ and dibasic cations such as Mg2+as a function of their importance in the interaction process.•Soil samples were collected from different land-use types in rural farming communities of the Upper Rio Grande Valley.•Samples were oven dried, disaggregated, sieved, treated with 10% HF, rinsed and oven dried.•Oven dried samples were subjected to Mid-infrared (4000-400 cm-1), XRD and ED-XRF analyses.

The impact of flash glucose monitoring on adults with type 1 Diabetes' eating habits and relationship with food.

AIM: To gain a better understanding of how the FreeStyle Libre (FSL) flash glucose monitor influences the eating habits and relationship with food of adults with type 1 diabetes (T1D). METHODS: Reflexive thematic analysis was conducted on fifteen semi-structured interviews conducted with adults with T1D, exploring their experiences of at least one year of FSL use. RESULTS: Four themes were constructed from the qualitative data: (1) Personal Food Story (what food represented before and after diabetes diagnosis), (2) New Opportunities (the FSL offered novel discoveries and increased self-confidence regarding food choices), (3) Body as a Machine (participants viewed their bodies as a collection of complex processes requiring continuous maintenance), and (4) re-evaluating Diabetes (participants expressed a shift in their expectations of themselves and their diabetes management). Although the FSL offered participants more freedom and flexibility with their eating, this was constrained by feeling forever under scrutiny from the data. CONCLUSIONS: Findings suggest the FSL influences users' eating habits, including when, why, what and how much they eat. Participants described both the positive and negative impact of these changes on their emotional wellbeing and relationship with diabetes, arguing for a need to address patients' relationship with food in routine clinic care.

FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis.

Rationale: Sarcoidosis is an inflammatory granulomatous disease of unknown etiology with predominant lung involvement. Organ involvement and disease severity, as well as the nature of immune alterations, vary among patients leading to a range of clinical phenotypes and outcomes. Our objective was to evaluate the association of disease course and immune responses in pulmonary sarcoidosis. Methods: In this prospective cohort study of 30 subjects, most of whom were followed for one year, we evaluated 14 inflammatory markers in plasma, 13 Treg/T cell flow cytometry markers and 8 parameters of FOXP3+ Treg biology, including suppressive function, epigenetic features and stability. Results: We identified a set of 13 immunological parameters that differ in sarcoidosis subjects in comparison with healthy donors. Five of those were inversely correlated with suppressive function of Tregs in sarcoidosis, and six (TNFα, TNFR I and II, sCD25, Ki-67 and number of Tregs) were particularly upregulated or increased in subjects with thoracic lymphadenopathy. Treg suppressive function was significantly lower in patients with thoracic lymphadenopathy, and in patients with higher burdens of pulmonary and systemic symptoms. A combination of five inflammatory markers, Ki-67 expression, Treg function, and lung diffusion capacity evaluated at study entry predicted need for therapy at one year follow-up in 90% of cases. Conclusion: Tregs may suppress ongoing inflammation at local and systemic levels, and TNFα, TNFR I and II, sCD25 and Ki-67 emerge as attractive biomarkers for in vivo sarcoid inflammatory activity.

Identification and Prognosis of Patients With Interstitial Pneumonia With Autoimmune Features.

BACKGROUND/OBJECTIVE: Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF. METHODS: We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models. RESULTS: We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77-11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome. CONCLUSION: Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors.

A CT Algorithm Can Elevate the Differential Diagnosis of Interstitial Lung Disease by Non-specialists to Equal That of Specialist Thoracic Radiologists.

BACKGROUND: Diagnosis of diffuse parenchymal lung diseases (DPLD) on high resolution CT (HRCT) is difficult for non-expert radiologists due to varied presentation for any single disease and overlap in presentation between diseases. RATIONALE AND OBJECTIVES: To evaluate whether a pattern-based training algorithm can improve the ability of non-experts to diagnosis of DPLD. MATERIALS AND METHODS: Five experts (cardiothoracic-trained radiologists), and 25 non-experts (non-cardiothoracic-trained radiologists, radiology residents, and pulmonologists) were each assigned a semi-random subset of cases from a compiled database of DPLD HRCTs. Each reader was asked to create a top three differential for each case. The non-experts were then given a pattern-based training algorithm for identifying DPLDs. Following training, the non-experts were again asked to create a top three differential for each case that they had previously evaluated. Accuracy between groups was compared using Chi-Square analysis. RESULTS: A total of 400 and 1450 studies were read by experts and non-experts, respectively. Experts correctly placed the diagnosis as the first item on the differential versus having the correct diagnosis as one of their top three diagnoses at an overall rate of 48 and 64.3%, respectively. Pre-training, non-experts achieved a correct diagnosis/top three of 32.5 and 49.7%, respectively. Post-training, non-experts demonstrated a correct diagnosis/top three of 41.2 and 65%, a statistically significant increase (p < 0.0001). In addition, post training, there was no difference between non-experts and experts in placing the correct diagnosis within their top three differential. CONCLUSION: The diagnosis of DPLDs by HRCT imaging alone is relatively poor. However, use of a pattern-based teaching algorithm can improve non-expert interpretation and enable non-experts to include the correct diagnosis within their differential diagnoses at a rate comparable to expert cardiothoracic trained radiologists.

PSICalc: a novel approach to identifying and ranking critical non-proximal interdependencies within the overall protein structure.

Motivation: AlphaFold has been a major advance in predicting protein structure, but still leaves the problem of determining which sub-molecular components of a protein are essential for it to carry out its function within the cell. Direct coupling analysis predicts two- and three-amino acid contacts, but there may be essential interdependencies that are not proximal within the 3D structure. The problem to be addressed is to design a computational method that locates and ranks essential non-proximal interdependencies within a protein involving five or more amino acids, using large, multiple sequence alignments (MSAs) for both globular and intrinsically unstructured proteins. Results: We developed PSICalc (Protein Subdomain Interdependency Calculator), a laptop-friendly, pattern-discovery, bioinformatics software tool that analyzes large MSAs for both structured and unstructured proteins, locates both proximal and non-proximal inter-dependent sites, and clusters them into pairwise (second order), third-order and higher-order clusters using a k-modes approach, and provides ranked results within minutes. To aid in visualizing these interdependencies, we developed a graphical user interface that displays these subdomain relationships as a polytree graph. To demonstrate, we provide examples of both proximal and non-proximal interdependencies documented for eukaryotic topoisomerase II including between the unstructured C-terminal domain and the N-terminal domain. Availability and implementation: https://github.com/jdeweeselab/psicalc-package. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Identifying the research priorities of healthcare professionals in UK vascular surgery: modified Delphi approach.

BACKGROUND: The Vascular Research Collaborative was established to develop a national research strategy for patients with vascular disease in the UK. This project aimed to establish national research priorities in this patient group. METHODS: A modified Delphi approach, an established method for reaching a consensus opinion among a group of experts in a particular field, was used to survey national multidisciplinary vascular clinical specialists. Two rounds of online surveys were conducted involving the membership of the Vascular Society, Society of Vascular Nurses, Society for Vascular Technology, and the Rouleaux Club (vascular surgical trainees). The first round invited any suggestions for vascular research topics. A steering group then collated and rationalized the suggestions, categorizing them by consensus into pathological topics and research categories, and amalgamating the various questions relating to the same fundamental issue into a single question. The second round involved recirculating these questions to the same participants for priority scoring. RESULTS: Round 1 resulted in 1231 suggested research questions from 481 respondents. Steering group collation and rationalization resulted in 83 questions for ranking in round 2. The second round resulted in a hierarchical list of vascular research priorities. The highest scoring priorities addressed topics related to critical lower-limb ischaemia, diabetic foot disease, amputation, wound healing, carotid plaque morphology, and service organization/delivery. CONCLUSION: It is anticipated that these results will drive the UK national vascular research agenda for the next 5-10 years. It will facilitate focused development and funding of new research projects in current clinical areas of unmet need where potential impact is greatest.

Crystal structure and specific location of a germin-like protein with proteolytic activity from Thevetia peruviana.

Peruvianin-I is a cysteine peptidase (EC 3.4.22) purified from Thevetia peruviana. Previous studies have shown that it is the only germin-like protein (GLP) with proteolytic activity described so far. In this work, the X-ray crystal structure of peruvianin-I was determined to a resolution of 2.15 Å (PDB accession number: 6ORM) and its specific location was evaluated by different assays. Its overall structure shows an arrangement composed of a homohexamer (a trimer of dimers) where each monomer exhibits a typical ß-barrel fold and two glycosylation sites (Asn55 and Asn144). Analysis of its active site confirmed the absence of essential amino acids for typical oxalate oxidase activity of GLPs. Details of the active site and molecular docking results, using a specific cysteine peptidase inhibitor (iodoacetamide), were used to discuss a plausible mechanism for proteolytic activity of peruvianin-I. Histological analyses showed that T. peruviana has articulated anastomosing laticifers, i.e., rows of cells which merge to form continuous tubes throughout its green organs. Moreover, peruvianin-I was detected exclusively in the latex. Because latex peptidases have been described as defensive molecules against insects, we hypothesize that peruvianin-I contributes to protect T. peruviana plants against herbivory.

Lower Respiratory Tract Infection with Human Metapneumovirus: Chest CT Imaging Features and Comparison with Other Viruses.

PURPOSE: Human metapneumovirus has been increasingly identified as a cause of lower respiratory tract infection in adults worldwide. The CT imaging features of human metapneumovirus in adults have not been characterized. The purpose of this paper is to determine the imaging features of human metapneumovirus and to compare them with features of other viruses. METHODS: Two clinicians retrospectively reviewed the medical records of 104 adults with lower respiratory tract infection due to human metapneumovirus at four hospitals in the northeast USA over 32 months. CT images were evaluated by two chest radiologists for airspace consolidation, bronchiectasis, bronchial wall thickening, ground-glass opacities, pleural effusion and tree-in-bud opacities and the dominant imaging pattern. Results for human metapneumovirus were compared with results previously reported for other viruses. RESULTS: Human metapneumovirus predominantly caused an airway-centric pattern (71-81/104, 68-77%) of infection characterized by bronchial wall thickening, tree-in-bud opacities, peri-bronchial consolidation and/or peri-bronchial ground-glass opacities. The airway-centric pattern has been previously reported with other paramyxoviridae (parainfluenza virus and respiratory syncytial virus). However, human metapneumovirus was significantly more likely (p = 0.03-0.001) to cause bronchopneumonia (46-55%) than parainfluenza virus (17%) or respiratory syncytial virus (21%). Follow-up CT in 41 (39%) patients with hMPV revealed resolution of findings in 38/41 (91%). CONCLUSION: The paramyxoviridae, including human metapneumovirus, are known to have a propensity to infect ciliated respiratory cells and we have demonstrated this leads to a propensity to cause bronchitis, bronchiolitis and bronchopneumonia on CT scans. Of these, human metapneumovirus is most likely to cause bronchopneumonia. Healthcare providers should consider human metapneumovirus as a cause of pneumonia on chest CT.

Impact of patient handover structure on neonatal perioperative safety.

OBJECTIVE: To compare the incidence, severity, preventability, and contributing factors of non-routine events-deviations from optimal care based on the clinical situation-associated with team-based, nurse-to-nurse, and mixed handovers in a large cohort of surgical neonates. STUDY DESIGN: A prospective observational study and one-time cross-sectional provider survey were conducted at one urban academic children's hospital. 130 non-cardiac surgical cases in 109 neonates who received pre- and post-operative NICU care. RESULTS: The incidence of clinician-reported NREs was high (101/130 cases, 78%) but did not differ significantly across acuity-tailored neonatal handover practices. National Surgical Quality Improvement-Pediatric occurrences of major morbidity were significantly higher (p < 0.001) in direct team handovers than indirect nursing or mixed handovers. CONCLUSIONS: NREs occur at a high rate and are of variable severity in neonatal perioperative care. NRE rates and contributory factors were homogenous across handover types. Surveyed clinicians recommend structured handovers for all patients at every transfer point regardless of acuity.

Structural and enzymatic characterization of Peruvianin­I, the first germin-like protein with proteolytic activity.

The germin-like protein (GLP) purified from Thevetia peruviana, Peruvianin-I, is the only one described as having proteolytic activity. Therefore, the goal of this study was to investigate the structural features responsible for its enzymatic activity. Although the amino acid sequence of Peruvianin-I showed high identity with other GLPs, it exhibited punctual mutations, which were responsible for the absence of oxalate oxidase activity. The phylogenetic analysis showed that Peruvianin-I does not belong to any classification of GLP subfamilies. Moreover, Peruvianin-I contains a catalytic triad found in all plant cysteine peptidases. Molecular docking simulations confirmed the role of the catalytic triad in its proteolytic activity. Synchrotron radiation circular dichroism assays confirmed that Peruvianin-I was stable at pH ranging from 5.0 to 8.0 and that it presented significant structural changes only above 60 °C. The addition of iodoacetamide caused changes in its native conformation, but only a slight effect was observed after adding a reducing agent. This study reports an unusual protein with germin-like structure, lacking typical oxalate oxidase activity. Instead, the proteolytic activity observed suggests that the protein is a cysteine peptidase. These structural peculiarities make Peruvianin­I an interesting model for further understanding of the action of laticifer fluids in plant defense.

Compliance with NICE guidelines when commissioning varicose vein procedures.

BACKGROUND: Varicose veins impair quality of life and can lead to chronic leg ulcers. National Institute for Health and Care Excellence (NICE) guidelines (CG168) set out evidence-based standards for patient management. In England, Clinical Commissioning Groups (CCGs) fund NHS care within their locality. The objective of this study was to evaluate CCGs' commissioning policies and compare them with CG168. METHODS: Searches were made for the published policies of all 206 English CCGs. They were reviewed for compliance with NICE guidelines and the associated quality standard. Areas of disagreement were analysed for themes. RESULTS: Some 203 CCGs (98·5 per cent) had a published policy and 190 (93·6 per cent) of these were published after publication of CG168. Only 73 of the policies (36·0 per cent) were compliant with CG168. Treatment was restricted on the basis of clinical disease severity in 119 CCGs (58·6 per cent); 29 (14·3 per cent) stipulated delay of treatment using a 'trial' of conservative treatment; 22 (10·8 per cent) used lifestyle-related factors such as BMI and smoking status to ration treatment. Treatment was commissioned for uncomplicated symptomatic varicose veins in 87 CCGs (42·9 per cent), but some applied additional rationing mechanisms; 109 CCGs (53·7 per cent) would treat oedema, 183 (90·1 per cent) would treat skin and soft tissue damage, 202 (99·5 per cent) healed ulceration, and all would allow active ulcers to be treated. DISCUSSION: The majority of CCGs in England have commissioning policies that contradict NICE guidelines. Rationing strategies include disease severity, delay and patient lifestyle-related factors, creating unwarranted geographical variation for varicose vein treatment, disregarding the NHS Constitution for England, and perhaps leading to an increase in costly treatment of chronic complications in the long term.

Long-term outcomes of endovenous laser ablation and conventional surgery for great saphenous varicose veins.

BACKGROUND: Clinical guidelines recommend endovenous laser ablation (EVLA) over surgery based on short-term evidence, yet there are few studies reporting mid- to long-term outcomes. The aim of this study was to report the 5-year outcomes from an RCT of surgery versus EVLA for treatment of symptomatic great saphenous varicose veins. METHODS: Patients with symptomatic varicose veins due to great saphenous vein (GSV) incompetence were followed up 5 years after enrolment in a randomized trial of either surgery (saphenofemoral junction ligation, GSV strip to the knee and multiple avulsions of varicosities) or EVLA plus multiple avulsions. Outcomes included: clinical recurrence, defined as new varicose veins greater than 3 mm in diameter; Venous Clinical Severity Score (VCSS); quality of life measured by means of Short Form 36, EuroQol Five Dimensions (EQ-5D™) and Aberdeen Varicose Vein Questionnaire (AVVQ); patient satisfaction; and duplex ultrasound examination (DUS) findings. RESULTS: Some 218 of the 276 patients enrolled in the trial (79·0 per cent) were available for follow-up. Clinical recurrence was more frequent following surgery than EVLA at 5 years (34·3 versus 20·9 per cent; P = 0·010). Both groups demonstrated sustained significant improvements at 5 years over baseline in VCSS (surgery: median (i.q.r.) 1 (0-2) from 4 (3-5), P < 0·001; EVLA: 0 (0-1) from 4 (3-5), P < 0·001), AVVQ (surgery: 4·59 (0·56-9·78) from 13·69 (9·81-18·11), P < 0·001; EVLA: 3·35 (0·17 to 6·55) from 12·73 (9·41-17·32), P < 0·001) and EQ-5D™ (surgery: 1·000 (0·796-1·000) from 0·859 (0·796-1·000), P = 0·002; EVLA: 1·000 (0·796-1·000) from 0·808 (0·796-1·000), P = 0·002). VCSS was better for EVLA than surgery at 5 years (P = 0·031). Technical success assessed by DUS remained high at 5 years (85·4 per cent for surgery and 93·2 per cent for EVLA; P = 0·074). DUS-detected anatomical patterns of recurrence differed between the groups. CONCLUSION: EVLA was more effective than surgery in preventing clinical recurrence 5 years after treatment of great saphenous varicose veins. Patient-reported outcome measures were similar. Registration number: NCT00759434 (http://www.clinicaltrials.gov).

Multiplexed precision genome editing with trackable genomic barcodes in yeast.

Our understanding of how genotype controls phenotype is limited by the scale at which we can precisely alter the genome and assess the phenotypic consequences of each perturbation. Here we describe a CRISPR-Cas9-based method for multiplexed accurate genome editing with short, trackable, integrated cellular barcodes (MAGESTIC) in Saccharomyces cerevisiae. MAGESTIC uses array-synthesized guide-donor oligos for plasmid-based high-throughput editing and features genomic barcode integration to prevent plasmid barcode loss and to enable robust phenotyping. We demonstrate that editing efficiency can be increased more than fivefold by recruiting donor DNA to the site of breaks using the LexA-Fkh1p fusion protein. We performed saturation editing of the essential gene SEC14 and identified amino acids critical for chemical inhibition of lipid signaling. We also constructed thousands of natural genetic variants, characterized guide mismatch tolerance at the genome scale, and ascertained that cryptic Pol III termination elements substantially reduce guide efficacy. MAGESTIC will be broadly useful to uncover the genetic basis of phenotypes in yeast.

Exposure to Ambient Particulate Matter Is Associated With Accelerated Functional Decline in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF. METHODS: We identified a cohort of subjects seen at a single university referral center from 2007 to 2013. Average concentrations of particulate matter < 10 and < 2.5 µg/m3 (PM10 and PM2.5, respectively) were assigned to each patient based on geocoded residential addresses. A linear multivariable mixed-effects model determined the association between the rate of decline in FVC and average PM concentration, controlling for baseline FVC at first measurement and other covariates. RESULTS: One hundred thirty-five subjects were included in the final analysis after exclusion of subjects missing repeated spirometry measurements and those for whom exposure data were not available. There was a significant association between PM10 levels and the rate of decline in FVC during the study period, with each µg/m3 increase in PM10 corresponding with an additional 46 cc/y decline in FVC (P = .008). CONCLUSIONS: Ambient air pollution, as measured by average PM10 concentration, is associated with an increase in the rate of decline of FVC in IPF, suggesting a potential mechanistic role for air pollution in the progression of disease.

Identification and characterization of two germin-like proteins with oxalate oxidase activity from Calotropis procera latex.

Germin-like proteins (GLPs) have been identified in several plant tissues. However, only one work describes GLP in latex fluids. Therefore, the goal of this study was to investigate GLPs in latex and get new insights concerning the structural and functional aspects of these proteins. Two complete sequences with high identity (>50%) with other GLPs, termed CpGLP1 and CpGLP2, were obtained and consecutively presented 216 and 206 amino acid residues, corresponding to molecular masses of 22.7 and 21.7kDa, pI 6.8 and 6.5. The three-dimensional models revealed overall folding similar to those reported for other plant GLPs. Both deduced sequences were grouped into the GER 2 subfamily. Molecular docking studies indicated a putative binding site consisting of three highly conserved histidines and a glutamate residue, which interacted with oxalate. This interaction was later supported by enzymatic assays. Superoxide dismutase (common activity in GLPs) was not detected for CpGLP1 and CpGLP2 by zymogram. The two proteins were detected in the latex, but not in non-germinated or germinated seeds and calli. These results give additional support that germin-like proteins are broadly distributed in plants and they are tissue-specific. This particularity deserves further studies to better understand their functions in latex.

Thoracic Manifestations of Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by venous malformations and a predisposition to pulmonary embolism. We reviewed the imaging findings of 7 adult patients with KTS who underwent thoracic CT. While the superficial manifestations of KTS predominantly affect the extremities, patients frequently develop abnormalities of the pulmonary arterial system, particularly chronic thromboembolic pulmonary hypertension. Additionally, some patients are seen to develop pulmonary arteriolar aneurysms; the physiologic significance of this finding is unknown at this time. Radiologists should be aware of these potential findings and have a high index of suspicion for chronic PE in patients with KTS.