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Vasodilator stress cardiovascular magnetic resonance (CMR) is a powerful diagnostic modality, but data toward its use in patients with permanent pacemakers (PPMs) or implantable cardioverter-defibrillators (ICDs) is limited.Patients with ICDs (1% pacing) or PPMs who underwent regadenoson single photon emission computed tomography (SPECT) and all patients with ICDs or PPMs who underwent stress CMR were retrospectively identified. SPECT tests were analyzed for hemodynamic responses and new pacing requirements; CMR studies were examined for safety, device characteristics and programming, hemodynamic responses, and image quality. Changes from baseline were evaluated with the Related-Samples Wilcoxon Signed Rank Test. Of 67 patients (median age 65 [IQR 58-72] years, 31 [46%] female, 31 [46%] Black), 47 underwent SPECT and 20 CMR. With regadenoson SPECT, 89% of patients experienced tachycardic responses above resting heart rates (+19 [13-32] beats per minute, p .01). During stress CMR, 10 (50%) devices were asynchronously paced approximately 10 beats per minute above resting rates, and the remaining were temporarily deactivated. Those with asynchronous pacing had no changes in heart rates, whereas patients with deactivated devices had near uniform heart rate accelerations. Image quality was diagnostic in the majority of stress CMR sequences, with nonconditional ICDs contributing 40 of 57 (70%) of nondiagnostic segments.This data supports the safety of vasodilator stress CMR with promising diagnostic quality images in patients with CMR conditional ICDs and PPMs. Despite a near uniform tachycardic response to regadenoson in the SPECT environment, high rates of asynchronous pacing during vasodilator stress CMR did not result in competitive pacing or adverse arrhythmic events. Further studies are needed to validate these findings and confirm the diagnostic and prognostic performance of stress CMR in these individuals.

The Illuminating the Druggable Genome (IDG) project aims to improve our understanding of understudied proteins and our ability to study them in the context of disease biology by perturbing them with small molecules, biologics, or other therapeutic modalities. Two main products from the IDG effort are the Target Central Resource Database (TCRD) (http://juniper.health.unm.edu/tcrd/), which curates and aggregates information, and Pharos (https://pharos.nih.gov/), a web interface for users to extract and visualize data from TCRD. Since the 2021 release, TCRD/Pharos has focused on developing visualization and analysis tools that help reveal higher-level patterns in the underlying data. The current iterations of TCRD and Pharos enable users to perform enrichment calculations based on subsets of targets, diseases, or ligands and to create interactive heat maps and UpSet charts of many types of annotations. Using several examples, we show how to address disease biology and drug discovery questions through enrichment calculations and UpSet charts.

Odontomas are benign odontogenic tumors subdivided morphologically into complex or compound odontomas. This paper describes the case of a complex odontoma in a 31-year-old male who complained of a painless swelling in right mandibular region which was diagnosed radiographically as complex odontome. Surgical enucleation of the lesion was done and sent for histopathological examination.

Macroscopic T-wave alternans (TWA) is a rare finding on surface electrocardiogram and has been associated with an increased risk of impending sudden cardiac death. We highlight a case of macroscopic TWA in a patient with markedly prolonged QTc interval preceding ventricular electrical storm, which was refractory to medical management. Autonomic modulation of the stellate ganglion resulted in improvement in both TWA and QTc interval. (Level of Difficulty: Advanced.), Central Illustration

The interatrial septum is a structure with complex embryological development. The true atrial septum is a circumscribed structure, and transgression outside of this area during transseptal puncture may result in entry into the extracardiac space or aorta that may result in a pericardial effusion or cardiac tamponade. (Level of Difficulty: Intermediate.), Graphical abstract

The reported success rate of His-bundle pacing (HBP) in patients with infranodal atrioventricular (AV) conduction disease is only 52%-76%. The success rate of left bundle branch area pacing (LBBAP) in this cohort is not well studied.The purpose of this study was to evaluate the feasibility, safety, and electrophysiological characteristics of LBBAP in patients with AV conduction disease.Patients with AV conduction disease referred for pacemaker implantation at 2 centers between February 2019 and June 2021 were considered for LBBAP. Baseline demographic characteristics, procedural success rates, electrophysiological parameters, and complications were assessed.LBBAP was successful in 340 of 364 patients (93%). Mean age was 72 ± 13 years, and mean follow-up was 331 ± 244 days. Pacing indications were Mobitz I in 27 patients (7%), Mobitz II or 2:1 AV block or high-grade AV block in 94 patients (26%), complete heart block in 199 patients (55%), and sick sinus syndrome with isolated bundle branch block in 44 patients (12%). Left bundle branch block and right bundle branch block were present in 57 patients (16%) and 140 patients (38%), respectively. Procedural success rates did not differ between indications (92.6%, 93.6%, 92.9%, and 95%, respectively) or between patients with narrow (120 ms) vs wide QRS (≥120 ms). Mean LBBAP threshold was 0.77 ± 0.34 V at 0.4 ms at implant and remained stable during follow-up. There were 4 (1.2%) acute LBBAP lead dislodgments.LBBAP is safe and feasible with high success rates for patients with AV conduction disease. In contrast to HBP, LBBAP success rates remain high over the entire spectrum of AV conduction disease, and lead parameters remain stable during follow-up.

Eosinophilic granulomatosis with polyangiitis, formerly Churg-Strauss Syndrome, is an uncommon disorder that carries a high mortality when coronary artery disease develops. Early recognition and treatment is crucial. We highlight an unusual presentation of acute coronary syndrome not associated with atherosclerotic coronary disease. (Level of Difficulty: Intermediate.), Graphical abstract, Eosinophilic granulomatosis with polyangiitis, formerly Churg-Strauss Syndrome, is an uncommon disorder that carries a high mortality when coronary…

PURPOSE OF REVIEW: Cardiovascular involvement in coronavirus disease 2019 (CoVID-19) is relatively common and portends an increased risk of morbidity and mortality. Manifestations of myocardial injury may exhibit significant overlap and result in diagnostic uncertainty. This review will summarize recent literature around cardiovascular complications of CoVID-19. RECENT FINDINGS: Venous thromboembolism, atrial fibrillation, and type II myocardial infarction are observed commonly in CoVID-19, while severe acute respiratory syndrome coronavirus 2 viral myocarditis remains quite rare. Although infrequent, CoVID-19 vaccination has been associated with myocarditis and pericarditis in young individuals. SUMMARY: Various forms of CoVID-19-related myocardial injury have been associated with increased utilization of mechanical ventilation, hemodynamic deterioration, and mortality. Manifestations of myocardial injury in CoVID-19 are varied, but share common drivers of illness including sequelae of sepsis, immune-mediated factors, and a prothrombotic state. Understanding the forms of myocardial injury in CoVID-19 may aid in rapid diagnosis and treatment.

Single-center studies have shown feasibility of conduction system pacing (CSP) via His-bundle pacing (HBP) or left bundle branch area pacing (LBBAP) in atrial fibrillation (AF) patients undergoing atrioventricular junction ablation (AVJA).The purpose of this study was to compare outcomes in patients with HBP and LBBAP leads undergoing AVJA.Consecutive patients with CSP leads referred for AVJA between October 2014 and May 2021 were included. Pacing lead characteristics, procedural characteristics, complications, and long-term outcomes were assessed.One hundred five AVJA procedures (55 HBP, 50 LBBAP) were performed in 98 patients (48 HBP, 50 LBBAP). The acute success rate of the AVJA procedure was 94% vs 100% (P = .11) in HBP vs LBBAP groups. Seven (14%) redo AVJA procedures were required in the HBP group. Mean procedural time (44 ± 24 min vs 34 ± 16 min; P = .02) and mean fluoroscopy time (16 ± 18 min vs 7 ± 6 min; P.001) were significantly longer in the HBP vs LBBAP group. An acute rise in threshold was noted in 8 cases (14.5%), and 4 (8%) developed exit block after AVJA in HBP patients. Chronic HBP threshold ≥2.5 V was seen in 23 patients (48%), and 4 (8%) HBP leads were deactivated. CSP preserved ejection fraction (EF) in the overall cohort (N = 70; 53% ± 10% vs 55% ± 10%; P = .09) and significantly improved in those with reduced EF50% at baseline (N = 16; 37% ± 7.6% vs 46% ± 13%; P = .02).AVJA in the presence of an LBBAP lead is associated with a higher success rate and fewer acute and chronic lead-related complications. CSP with either HBP or LBBAP preserves left ventricular systolic function in patients with refractory atrial fibrillation post AVJA.

Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions., HuBMAP supports technology development, data acquisition, and spatial analyses to generate comprehensive molecular and cellular three-dimensional tissue maps.

In early stage buccal mucosa carcinoma, in spite of successful curative surgery, the health-related quality-of-life (HRQoL) may not improve. We aimed to study HRQoL in these patients who had undergone successful curative surgery and determined factors that influence the HRQoL. Subjects, aged 18–70 years, who had undergone successful curative surgery for stage I and II buccal mucosa cancer, were assessed for HRQoL using the University of Washington Quality of Life Questionnaire and factors affecting HRQoL were determined. Their scores were compared with normative reference scores. 54 patients (stages I 54%, II 46%) aged 44 ± 11 years (87% males) were studied. They had undergone curative surgery a median of 8.5 (IQR 4–13.5) months ago. Their mean global HRQoL score was 77 ± 30, with significantly poorer scores compared to reference in domains of appearance, activity, swallowing, chewing, speech, shoulder, saliva, mood and anxiety. Anxiety, activity, and chewing were considered the most important domains by the patients. Among the factors influencing HRQoL, duration since surgery was the most important factor, and patients with recent surgery had worse performance in chewing, saliva and mood. Patients with stage II had worse performance in shoulder and anxiety compared to stage I. Post-operative radiotherapy worsened swallowing and shoulder function. In spite of successful curative surgery for buccal mucosa carcinoma, the HRQoL continues to remain sub-optimal with poor scores in most of the domains. These domains must be focused on with appropriate measures in order to improve overall HRQoL in patients after successful curative surgery.

Malaria parasites activate a broad-selectivity ion channel on their host erythrocyte membrane to obtain essential nutrients from the bloodstream. This conserved channel, known as the plasmodial surface anion channel (PSAC), has been linked to parasite clag3 genes in P. falciparum, but epigenetic switching between the two copies of this gene hinders clear understanding of how the encoded protein determines PSAC activity. Here, we used linkage analysis in a P. falciparum cross where one parent carries a single clag3 gene to overcome the effects of switching and confirm a primary role of the clag3 product with high confidence. Despite Mendelian inheritance, CLAG3 conditional knockdown revealed remarkably preserved nutrient and solute uptake. Even more surprisingly, transport remained sensitive to a CLAG3 isoform-specific inhibitor despite quantitative knockdown, indicating that low doses of the CLAG3 transgene are sufficient to confer block. We then produced a complete CLAG3 knockout line and found it exhibits an incomplete loss of transport activity, in contrast to rhoph2 and rhoph3, two PSAC-associated genes that cannot be disrupted because nutrient uptake is abolished in their absence. Although the CLAG3 knockout did not incur a fitness cost under standard nutrient-rich culture conditions, this parasite could not be propagated in a modified medium that more closely resembles human plasma. These studies implicate oligomerization of CLAG paralogs encoded by various chromosomes in channel formation. They also reveal that CLAG3 is dispensable under standard in vitro conditions but required for propagation under physiological conditions., Author summary Malaria, a globally important infectious disease, is caused by parasites that invade and grow in circulating red blood cells to avoid host immune attack. Infected red blood cells have increased uptake of diverse nutrients, fueling parasite growth; this uptake is mediated by an ion channel that transports essential nutrients across the red blood cell membrane. Three proteins made by the parasite have been linked to this channel, but how they increase uptake is unknown. Here, we used mapping in a genetic cross of two strains of the virulent human malaria parasite to confirm a primary role of one protein known as CLAG3. We then used gene editing to produce a parasite that has reduced CLAG3 levels when a stabilizing chemical is removed; surprisingly, solute transport was minimally changed despite a 90% reduction in CLAG3. Gene editing was also used to make a parasite without any CLAG3. This knockout parasite had reduced nutrient uptake, but it still grew normally in media with high nutrient levels; it was unable to grow when nutrient levels were lowered to levels like those in the human bloodstream. The complex effects of channel inhibitors on these genetically modified parasites suggests that CLAG3 and the two other proteins interact with each other to form large protein clusters in the red blood cell membrane; these clusters may form the nutrient uptake pore. Our studies indicate that CLAG3 is required for parasite survival and growth in the bloodstream and that the channel it produces can be targeted to make new antimalarial drugs.

Objective Inflammation in adipose tissues in obesity promotes insulin resistance and metabolic disease. The Duffy antigen receptor for chemokines (DARC) is a promiscuous non-signaling receptor expressed on erythrocytes and other cell types that modulates tissue inflammation by binding chemokines such as monocyte chemoattractant protein-1 (MCP-1) and by acting as a chemokine reservoir. DARC allelic variants are common in humans, but the role of DARC in modulating obesity-related metabolic disease is unknown. Methods We examined body weight gain, tissue adiposity, metabolic parameters and inflammatory marker expression in wild-type and DARC knockout mice fed a chow diet (CD) and high fat diet (HFD). Results Compared to wild-type mice, HFD-fed DARC knockout mice developed glucose intolerance and insulin resistance independent of increases in body weight or adiposity. Interestingly, insulin sensitivity was also diminished in lean male DARC knockout mice fed a chow diet. Insulin production was not reduced by DARC gene deletion, and plasma leptin levels were similar in HFD fed wild-type and DARC knockout mice. MCP-1 levels in plasma rose significantly in the HFD fed wild-type mice, but not in the DARC knockout mice. Conversely, adipose tissue MCP-1 levels were higher, and more macrophage crown-like structures were detected, in the HFD fed DARC knockout mice as compared with the wild-type mice, consistent with augmented adipose tissue inflammation that is not accurately reflected by plasma levels of DARC-bound MCP-1 in these mice. Conclusions These findings suggest that DARC regulates metabolic function and adipose tissue inflammation, which may impact obesity-related disease in ethnic populations with high frequencies of DARC allelic variants.

Three-dimensional (3-D) printing is a method of manufacturing in which materials like plastic or metal are deposited onto one another in layers to produce a 3-D object. Because of the complex anatomy of craniomaxillofacial structures, full recovery of craniomaxillofacial tissues from trauma, surgeries, or congenital malformations is extremely challenging. 3-D printing of scaffolds, tissue analogs, and organs has been proposed as an exciting alternative to address some of these key challenges in craniomaxillofacial surgery. There are four broad types of 3-D printing surgical applications that can be used in craniomaxillofacial surgery: contour models (positive-space models to allow preapplication of hardware before surgery), guides (negative-space models of actual patient data to guide cutting and drilling), splints (negative-space models of virtual postoperative positions to guide final alignment), and implants (negative-space 3-D printed implantable materials or 3-D printed molds into which nonprintable materials are poured). 3-D printing technology is being successfully used for surgeries for head and neck malignancies, mandibular reconstruction, orthognathic surgeries, for mandibulectomies after osteoradionecrosis, orbital floor fracture surgeries, nasal reconstruction, and cranioplasties. The excitement behind 3-D printing continues to increase and hopefully will drive improvements in the technology and its surgical applications, especially in craniomaxillofacial region. This present review sets out to explore use of 3-D printing technologies in craniomaxillofacial surgery.

The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability.

The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data analytics tools to improve our understanding of human diseases at the systems level. In contrast to other large-scale data generation efforts, LINCS Data and Signature Generation Centers (DSGCs) employ a wide range of assay technologies cataloging diverse cellular responses. Integration of, and unified access to LINCS data has therefore been particularly challenging. The Big Data to Knowledge (BD2K) LINCS Data Coordination and Integration Center (DCIC) has developed data standards specifications, data processing pipelines, and a suite of end-user software tools to integrate and annotate LINCS-generated data, to make LINCS signatures searchable and usable for different types of users. Here, we describe the LINCS Data Portal (LDP) (http://lincsportal.ccs.miami.edu/), a unified web interface to access datasets generated by the LINCS DSGCs, and its underlying database, LINCS Data Registry (LDR). LINCS data served on the LDP contains extensive metadata and curated annotations. We highlight the features of the LDP user interface that is designed to enable search, browsing, exploration, download and analysis of LINCS data and related curated content.

Peri-procedural management of dual antiplatelet therapy following percutaneous coronary intervention for esophagogastroduodenoscopy and intervention is not clearly defined. We describe a case of a patient with a drug-eluting stent implanted in the setting of an acute myocardial infarction six weeks earlier who was bridged with cangrelor after interruption of ticagrelor for esophageal balloon dilatation because of dysphagia. The patient tolerated the procedure well and was transitioned back to ticagrelor without any complications.