Coronary Artery Spasm-Related Heart Failure Syndrome: Literature Review.

Although heart failure (HF) is a clinical syndrome that becomes worse over time, certain cases can be reversed with appropriate treatments. While coronary artery spasm (CAS) is still underappreciated and may be misdiagnosed, ischemia due to coronary artery disease and CAS is becoming the single most frequent cause of HF worldwide. CAS could lead to syncope, HF, arrhythmias, and myocardial ischemic syndromes such as asymptomatic ischemia, rest and/or effort angina, myocardial infarction, and sudden death. Albeit the clinical significance of asymptomatic CAS has been undervalued, affected individuals compared with those with classic Heberden's angina pectoris are at higher risk of syncope, life-threatening arrhythmias, and sudden death. As a result, a prompt diagnosis implements appropriate treatment strategies, which have significant life-changing consequences to prevent CAS-related complications, such as HF. Although an accurate diagnosis depends mainly on coronary angiography and provocative testing, clinical characteristics may help decision-making. Because the majority of CAS-related HF (CASHF) patients present with less severe phenotypes than overt HF, it underscores the importance of understanding risk factors correlated with CAS to prevent the future burden of HF. This narrative literature review summarises and discusses separately the epidemiology, clinical features, pathophysiology, and management of patients with CASHF.

High-throughput lensless whole slide imaging via continuous height-varying modulation of a tilted sensor.

We report a new, to the best of our knowledge, lensless microscopy configuration by integrating the concepts of transverse translational ptychography and defocus multi-height phase retrieval. In this approach, we place a tilted image sensor under the specimen for introducing linearly increasing phase modulation along one lateral direction. Similar to the operation of ptychography, we laterally translate the specimen and acquire the diffraction images for reconstruction. Since the axial distance between the specimen and the sensor varies at different lateral positions, laterally translating the specimen effectively introduces defocus multi-height measurements while eliminating axial scanning. Lateral translation further introduces sub-pixel shift for pixel super-resolution imaging and naturally expands the field of view for rapid whole slide imaging. We show that the equivalent height variation can be precisely estimated from the lateral shift of the specimen, thereby addressing the challenge of precise axial positioning in conventional multi-height phase retrieval. Using a sensor with 1.67 µm pixel size, our low-cost and field-portable prototype can resolve the 690 nm linewidth on the resolution target. We show that a whole slide image of a blood smear with a 120mm2 field of view can be acquired in 18 s. We also demonstrate accurate automatic white blood cell counting from the recovered image. The reported approach may provide a turnkey solution for addressing point-of-care and telemedicine-related challenges.

Association between Coronary Artery Spasm and the risk of incident Diabetes: A Nationwide population-based Cohort Study.

Background: Non-diabetic coronary artery spasm (CAS) without obstructive coronary artery disease increases insulin resistance. We investigated the risk of incident type 2 diabetes (diabetes) associated with CAS. Methods: Patient records were retrospectively collected from the Taiwan National Health Insurance Research Database during the period 2000-2012. The matched cohorts consisted of 12,413 patients with CAS and 94,721 patients in the control group. Results: During the entire follow-up, the incidence of newly-diagnosed diabetes was 22.2 events per 1000 person-years in the CAS group and 13.9 events per 1000 person-years in the control group. The increased risk of CAS-related incident diabetes was observed regardless of sex and length of follow-up. The median time to incident diabetes was 2.9 and 3.5 years in the CAS and the control group (P <0.001), respectively, regardless of sex. Although age did not affect the risk of CAS-related incident diabetes, the risk was less apparent in the subgroups of male, dyslipidemia, chronic obstructive pulmonary disease, stroke, gout and medicated hypertension. However, CAS patients aged <50 years compared with patients ≥50 years had a greater risk of incident diabetes in females but not in males. Older CAS patients developed diabetes in a shorter length of time than younger patients. Conclusion: CAS is a risk factor for incident diabetes regardless of sex. However, females aged <50 years have a more apparent risk for CAS-related diabetes than old females, which is not observed in males. The median time of 2.9 years to incident diabetes warrants close follow-up.

A histone H4 lysine 20 methyltransferase couples environmental cues to sensory neuron control of developmental plasticity.

Animals change developmental fates in response to external cues. In the nematode Caenorhabditis elegans, unfavorable environmental conditions induce a state of diapause known as dauer by inhibiting the conserved DAF-2 insulin-like signaling (ILS) pathway through incompletely understood mechanisms. We have previously established a role for the C. elegans dosage compensation protein DPY-21 in the control of dauer arrest and DAF-2 ILS. Here, we show that the histone H4 lysine 20 methyltransferase SET-4, which also influences dosage compensation, promotes dauer arrest in part by repressing the X-linked ins-9 gene, which encodes a new agonist insulin-like peptide (ILP) expressed specifically in the paired ASI sensory neurons that are required for dauer bypass. ins-9 repression in dauer-constitutive mutants requires DPY-21, SET-4 and the FoxO transcription factor DAF-16, which is the main target of DAF-2 ILS. By contrast, autosomal genes encoding major agonist ILPs that promote reproductive development are not repressed by DPY-21, SET-4 or DAF-16/FoxO. Our results implicate SET-4 as a sensory rheostat that reinforces developmental fates in response to environmental cues by modulating autocrine and paracrine DAF-2 ILS.

Myocardial Ischemic Syndromes, Heart Failure Syndromes, Electrocardiographic Abnormalities, Arrhythmic Syndromes and Angiographic Diagnosis of Coronary Artery Spasm: Literature Review.

In coronary artery spasm (CAS), an excess coronary vasoconstriction causing total or subtotal vessel occlusion could lead to syncope, heart failure syndromes, arrhythmic syndromes, and myocardial ischemic syndromes including asymptomatic myocardial ischemia, stable and unstable angina, acute myocardial infarction, and sudden cardiac death. Although the clinical significance of CAS has been underrated because of the frequent absence of symptoms, affected patients appear to be at higher risk of syncope, serious arrhythmias, and sudden death than those with classic Heberden's angina pectoris. Therefore, a prompt diagnosis has important therapeutic implications, and is needed to avoid CAS-related complications. While a definitive diagnosis is based mainly on coronary angiography and provocative testing, clinical features may help guide decision-making. We perform a literature review to assess the past and current state of knowledge regarding the clinical features, electrocardiographic abnormalities and angiographic diagnosis of CAS, while a discussion of mechanisms is beyond the scope of this review.

Coronary Artery Spasm as Related to Anxiety and Depression: A Nationwide Population-Based Study.

OBJECTIVE: Anxiety and depression are risk factors for obstructive coronary artery disease (CAD), but their effects on coronary artery spasm (CAS) remain unestablished. METHODS: Patient records in this population-based study were retrospectively collected from the Taiwan National Health Insurance Research Database. Using propensity score matching, we used 1:1:1 ratio stratification into a control group of 10,325 individuals without CAS or CAD, a CAS group comprising 10,473 patients, and a CAD group comprising 10,473 patients during 2000-2012. RESULTS: The prevalence of CAS and CAD was 0.067% and 8.7%, respectively, in the general population. The prevalence of anxiety and depression diagnoses was significantly higher in patients with new-onset CAS than in those with new-onset CAD and controls without CAS/CAD, even after propensity score matching. Compared with CAD, anxiety and depression diagnoses conferred a higher risk of developing CAS (odds ratio [OR] = 2.29, 95% confidence interval [CI], 2.14-2.45, p < .001, and OR = 1.34, 95% CI, 1.08-1.66, p = .007, respectively). The association was even stronger when comparing CAS with the control group without CAD or CAS (OR = 5.20, 95% CI, 4.72-5.74, p < .001, and OR = 1.98, 95% CI, 1.50-2.62, p < .001, respectively). The increased risk of new-onset CAS as related to previous anxiety and depression diagnoses was comparable between males and females. CONCLUSIONS: Compared with CAD or the general population, anxiety and depression diagnoses confer a higher risk of developing CAS. No sex differences are found for the association of anxiety and depression with CAS.

TATN-1 mutations reveal a novel role for tyrosine as a metabolic signal that influences developmental decisions and longevity in Caenorhabditis elegans.

Recent work has identified changes in the metabolism of the aromatic amino acid tyrosine as a risk factor for diabetes and a contributor to the development of liver cancer. While these findings could suggest a role for tyrosine as a direct regulator of the behavior of cells and tissues, evidence for this model is currently lacking. Through the use of RNAi and genetic mutants, we identify tatn-1, which is the worm ortholog of tyrosine aminotransferase and catalyzes the first step of the conserved tyrosine degradation pathway, as a novel regulator of the dauer decision and modulator of the daf-2 insulin/IGF-1-like (IGFR) signaling pathway in Caenorhabditis elegans. Mutations affecting tatn-1 elevate tyrosine levels in the animal, and enhance the effects of mutations in genes that lie within the daf-2/insulin signaling pathway or are otherwise upstream of daf-16/FOXO on both dauer formation and worm longevity. These effects are mediated by elevated tyrosine levels as supplemental dietary tyrosine mimics the phenotypes produced by a tatn-1 mutation, and the effects still occur when the enzymes needed to convert tyrosine into catecholamine neurotransmitters are missing. The effects on dauer formation and lifespan require the aak-2/AMPK gene, and tatn-1 mutations increase phospho-AAK-2 levels. In contrast, the daf-16/FOXO transcription factor is only partially required for the effects on dauer formation and not required for increased longevity. We also find that the controlled metabolism of tyrosine by tatn-1 may function normally in dauer formation because the expression of the TATN-1 protein is regulated both by daf-2/IGFR signaling and also by the same dietary and environmental cues which influence dauer formation. Our findings point to a novel role for tyrosine as a developmental regulator and modulator of longevity, and support a model where elevated tyrosine levels play a causal role in the development of diabetes and cancer in people.

Whole genome sequencing and the transformation of C. elegans forward genetics.

Forward genetics has been an undeniably powerful approach in Caenorhabditis elegans and other model organisms. However, the trek from mutant isolation to identification of the causative molecular lesion can be time-consuming and fraught with obstacles. This has changed with the advent of whole genome sequencing (WGS). The widespread availability of high-throughput sequencing technology, coupled with the increasing affordability of WGS, has enabled the routine use of WGS in the analysis of forward genetic screens. The noteworthy development of one-step mapping/sequencing approaches has largely eliminated the bottleneck of conventional high-resolution mapping, greatly accelerating the journey from mutagenesis to gene discovery. By enabling the use of increasingly complex and diverse genetic backgrounds as substrates for mutagenesis, WGS is expanding the landscape of biological problems that can be interrogated using forward genetic approaches in C. elegans and other organisms.

Coronary artery spasm: review and update.

Coronary artery spasm (CAS), an intense vasoconstriction of coronary arteries that causes total or subtotal vessel occlusion, plays an important role in myocardial ischemic syndromes including stable and unstable angina, acute myocardial infarction, and sudden cardiac death. Coronary angiography and provocative testing usually is required to establish a definitive diagnosis. While the mechanisms underlying the development of CAS are still poorly understood, CAS appears to be a multifactorial disease but is not associated with the traditional risk factors for coronary artery disease. The diagnosis of CAS has important therapeutic implications, as calcium antagonists, not ß-blockers, are the cornerstone of medical treatment. The prognosis is generally considered benign; however, recurrent episodes of angina are frequently observed. We provide a review of the literature and summarize the current state of knowledge regarding the pathogenesis of CAS.

Current Trends in the Use of Buccal Grafts During Urethroplasty Among Society of Genitourinary Reconstructive Surgeons.

OBJECTIVE: To analyze current standards in urethroplasty by urologists employing buccal mucosal grafts (BMG) for treating urethral stricture disease (USD). METHODS: An IRB-approved online survey was distributed to members of the Society of Genitourinary Reconstructive Surgeons (GURS) between July and October 2022 to assess BMG utilization in urethroplasty. Questions covered surgeon experience, graft harvest site, graft length, surgical technique, and perceived success rates. RESULTS: Of 350 invited GURS members, 134 responded (38%). Sixty-nine percentage were GURS fellowship-trained, performing 10-30 urethroplasties annually. Ninety-five percentage harvested their own grafts, with 99% preferring buccal mucosa as the primary site. Buccal mucosa was favored over fasciocutaneous flap for penile urethroplasty, regardless of circumcision status (95% with, 84% without). For bulbar urethroplasty with BMG, dorsal graft placement was favored (66%) over ventral (34%). Most surgeons (90%) preferred multiple BMGs over combined graft/flap for panurethral strictures. When harvesting long grafts, 56% preferred using both cheeks. Anastomotic urethroplasty was preferred over buccal graft urethroplasty for short bulbomembranous stenosis post-radiotherapy (63% vs 37%). Surgeons reported a success rate of 80%-90% (53%). CONCLUSION: The expanded scope of reconstructive urology has led to increased use of BMG in diverse urethral reconstructions. Buccal grafts are now preferred for penile, bulbar, and panurethral strictures, demonstrating high perceived success rates in the reconstructive community.

Is it time to reduce the length of postgraduate training for physician-scientists in internal medicine?

Physician-scientists play a crucial role in advancing medical knowledge and patient care, yet the long periods of time required to complete training may impede expansion of this workforce. We examined the relationship between postgraduate training and time to receipt of NIH or Veterans Affairs career development awards (CDAs) for physician-scientists in internal medicine. Data from NIH RePORTER were analyzed for internal medicine residency graduates who received specific CDAs (K08, K23, K99, or IK2) in 2022. Additionally, information on degrees and training duration was collected. Internal medicine residency graduates constituted 19% of K awardees and 28% of IK2 awardees. Of MD-PhD internal medicine-trained graduates who received a K award, 92% received a K08 award; of MD-only graduates who received a K award, a majority received a K23 award. The median time from medical school graduation to CDA was 9.6 years for K awardees and 10.2 years for IK2 awardees. The time from medical school graduation to K or IK2 award was shorter for US MD-PhD graduates than US MD-only graduates. We propose that the time from medical school graduation to receipt of CDAs must be shortened to accelerate training and retention of physician-scientists.

Ovarian steroid cell tumor with biallelic adenomatous polyposis coli inactivation in a patient with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome that accounts for approximately 0.5-1% of all colorectal cancer cases. It is caused by germline mutations in the gene encoding the adenomatous polyposis coli (APC) tumor suppressor. Somatic APC inactivation due to mutation or loss of heterozygosity (LOH) promotes the development of adenomatous polyps by stabilizing the transcriptional coactivator ß-catenin. Although colorectal cancer is by far the most common malignancy seen in FAP patients, the widespread use of prophylactic colectomy in these patients has increased the clinical importance of extracolonic tumors that are part of the neoplastic spectrum in FAP. Many of these tumors exhibit LOH or somatic APC mutation, strongly supporting a causative role of APC inactivation in their pathogenesis. Here we describe a 47-year-old female FAP patient with clinical manifestations of virilization who was found to have an ovarian steroid cell tumor, a rare neoplasm not known to be associated with FAP. Immunohistochemical analysis of the ovarian tumor demonstrated strong nuclear ß-catenin staining consistent with somatic APC inactivation, and molecular analysis confirmed biallelic APC inactivation in the tumor. Our findings provide the first evidence that ovarian steroid cell tumors may be an extracolonic manifestation of FAP and implicate ß-catenin activation as an oncogenic mechanism in ovarian steroid cell tumorigenesis.

SARS-CoV-2: Current Tools to Fight COVID-19 ST-Elevation Myocardial Infarction.

The capacity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to wreak havoc on the inflammatory and coagulation pathways via the cytokine storm has led to over 6.3 million fatalities globally. Based on recent data, the mechanism predominately involves the formation of microvascular thrombosis when pertaining to cardiovascular disease. However, a subset of coronavirus disease-2019 (COVID-19)-positive patients present emergently with acute ST-elevation myocardial infarction (STEMI) are found to have severe epicardial thrombosis which is refractory to traditional coronary revascularization. We have noted mortality in these patients presenting to our facility to be as high as 90% and all angiographically confirmed to have thrombus which was refractory to traditional therapy. We present a case series of COVID-19-positive patients presenting with STEMI found to have epicardial thrombus who were treated with different traditional STEMI therapies but with fatal outcomes. Other possible techniques including mechanical thrombectomy, optimizing traditional and nontraditional anticoagulation therapy with the use of early hemodynamic support may prove more efficacious to destroy thrombus and potentially improve mortality.

Adjuvant Radiation and Survival Following Surgical Resection of Sinonasal Adenocarcinoma.

OBJECTIVES: This study aims to investigate the utility of adjuvant radiation in patients who undergo surgical resection for the management of node-negative sinonasal adenocarcinoma (SNAC). STUDY DESIGN: Retrospective database review. METHODS: The 2004-2016 National Cancer Data Base (NCDB) was used to extract patients with surgically resected node-negative SNAC. Kaplan-Meier survival analysis and Cox-Proportional Hazards Modelling were used to analyze the impact of adjuvant radiation on overall survival (OS) following surgery. RESULTS: 349 patients with SNAC underwent surgical resection. Of these patients, 154 (44.1%) received adjuvant radiotherapy (RT). Although there was no significant difference in race, age, or sex of those receiving RT, those receiving RT have more advanced diseases and are more likely to have positive margins. Kaplan Meier analysis showed no significant difference in 5-year OS in patient who received adjuvant RT in comparison to those who underwent surgical resection alone (65.7% vs. 72.6%, respectively; p = 0.378). In addition, when looking at only patients with positive margins, 5-year OS still did not have a significant difference (73.8% vs. 61.6%, respectively; p = 0.101). Only patients with clinical AJCC T4 showed a statistically significant survival benefit with adjuvant RT (56.9% vs. 29.9%, respectively; p = 0.009). CONCLUSIONS: Adjuvant RT does not appear to provide a significant survival benefit in patients with resected SNAC, with the exception of those with clinically AJCC T4 disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2603-2612, 2023.

Structural insights into the career path between pre- and postgraduate physician-scientist training programs.

The growing complexities of clinical medicine and biomedical research have clouded the career path for physician-scientists. In this perspective piece, we address one of the most opaque career stage transitions along the physician-scientist career path, the transition from medical school to research-focused internal medicine residency programs, or physician-scientist training programs (PSTPs). We present the perspectives of medical scientist training program (MSTP) and PSTP directors on critical features of PSTPs that can help trainees proactively align their clinical and scientific training for successful career development. We aim to provide both trainees and MSTP directors with a conceptual framework to better understand and navigate PSTPs. We also offer interview-specific questions to help trainees gather data and make informed decisions in choosing a residency program that best supports their career.

Three-Year Outcomes After Bifurcation Stenting With Zotarolimus-Eluting Stents: Final Results From the RESOLUTE ONYX Postapproval Study.

Background: Bifurcation represents a challenging lesion subset for percutaneous coronary intervention. Methods: In this prospective study of the Resolute Onyx zotarolimus-eluting stent (ZES), patients with a single bifurcation target lesion who underwent planned treatment using a provisional stenting technique were enrolled at 25 centers in the United States and Europe. The primary end point was target-vessel failure (TVF) at 1 year, and follow-up was performed through 3 years. Results: A total of 205 patients were enrolled. Mean age was 66.6 ± 10.7 years, 21.5% of patients were female, and diabetes mellitus was present in 30.2%. A provisional approach with a single stent was performed in 96.6% of patients. The rate of TVF at 1 year was 7.4%, fulfilling the prespecified performance criterion (upper 1-sided 95% CI of 11.1%, compared with the performance goal of 24.5%). At 3-year follow-up, the rate of TVF was 12.1%, the rate of clinically driven target-lesion revascularization was 6.0%, and there were no episodes of stent thrombosis related to the target lesion. Event rates were consistent among the cohort of patients with angiographic core laboratory-confirmed bifurcation lesions. Conclusions: In this prospective, multicenter study, bifurcation lesion treatment with Resolute Onyx ZES using a planned provisional stent approach was associated with favorable clinical outcomes through 3 years. These results support the longer-term safety and effectiveness of Resolute Onyx ZES to treat bifurcation lesions that are amenable to a planned provisional stenting technique.

Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions.

The relationships between oxidation-specific epitopes (OSE) and lipoprotein (a) [Lp(a)] and progressive atherosclerosis and plaque rupture have not been determined. Coronary artery sections from sudden death victims and carotid endarterectomy specimens were immunostained for apoB-100, oxidized phospholipids (OxPL), apo(a), malondialdehyde-lysine (MDA), and MDA-related epitopes detected by antibody IK17 and macrophage markers. The presence of OxPL captured in carotid and saphenous vein graft distal protection devices was determined with LC-MS/MS. In coronary arteries, OSE and apo(a) were absent in normal coronary arteries and minimally present in early lesions. As lesions progressed, apoB and MDA epitopes did not increase, whereas macrophage, apo(a), OxPL, and IK17 epitopes increased proportionally, but they differed according to plaque type and plaque components. Apo(a) epitopes were present throughout early and late lesions, especially in macrophages and the necrotic core. IK17 and OxPL epitopes were strongest in late lesions in macrophage-rich areas, lipid pools, and the necrotic core, and they were most specifically associated with unstable and ruptured plaques. Specific OxPL were present in distal protection devices. Human atherosclerotic lesions manifest a differential expression of OSEs and apo(a) as they progress, rupture, and become clinically symptomatic. These findings provide a rationale for targeting OSE for biotheranostic applications in humans.

Implantable ICP monitor for improved hydrocephalus management.

BACKGROUND: Hydrocephalus patients are commonly treated by insertion of ventriculoperitoneal shunts, but these have high complication rates. Monitoring of shunt and patient condition can be achieved through measuring intracranial pressure (ICP). Significant zero drift has limited previous developments towards a long-term implantable ICP monitor. We present a new implantable solid-state pressure sensor system appropriate for chronic (lifetime) monitoring of ICP. MATERIALS AND METHODS: Initial designs of the proposed ICP system were realised and the pressure sensor catheter underwent bench-top tests to analyse its characteristics. A drift rig was constructed for the long-term analysis of the sensor's zero drift. The pressure sensor catheter was used to continuously monitor blood pressure in rats. RESULTS: Three potential design solutions were realised: a standalone sensor, the sensor unit in line with a shunt system, and the sensor unit fully integrated into the shunt valve housing. Initial stability results across 46 days show a maximum drift of less than 2 mmHg and a minimum drift of less than 0.2 mmHg. CONCLUSION: Initial experience with the new implantable solid-state pressure sensor system confirms its suitability for chronic pressure monitoring. The device is promising for providing vital information on shunt and patient condition.

Apolipoprotein (a)/Lipoprotein(a)-Induced Oxidative-Inflammatory α7-nAChR/p38 MAPK/IL-6/RhoA-GTP Signaling Axis and M1 Macrophage Polarization Modulate Inflammation-Associated Development of Coronary Artery Spasm.

OBJECTIVE: Apolipoprotein (a)/lipoprotein(a) (Lp(a)), a major carrier of oxidized phospholipids, and α7-nicotinic acetylcholine receptor (α7-nAChR) may play an important role in the development of coronary artery spasm (CAS). In CAS, the association between Lp(a) and the α7-nAChR-modulated inflammatory macrophage polarization and activation and smooth muscle cell dysfunction remains unknown. METHODS: We investigated the relevance of Lp(a)/α7-nAChR signaling in patient monocyte-derived macrophages and human coronary artery smooth muscle cells (HCASMCs) using expression profile correlation analyses, fluorescence-assisted cell sorting flow cytometry, immunoblotting, quantitative real-time polymerase chain reaction, and clinicopathological analyses. RESULTS: There are increased serum Lp(a) levels (3.98-fold, p = 0.011) and macrophage population (3.30-fold, p = 0.013) in patients with CAS compared with patients without CAS. Serum Lp(a) level was positively correlated with high-sensitivity C-reactive protein (r 2 = 0.48, p < 0.01), IL-6 (r 2 = 0.38, p = 0.03), and α7-nAChR (r 2 = 0.45, p < 0.01) in patients with CAS, but not in patients without CAS. Compared with untreated or low-density lipoprotein- (LDL-) treated macrophages, Lp(a)-treated macrophages exhibited markedly enhanced α7-nAChR mRNA expression (p < 0.01) and activity (p < 0.01), in vitro and ex vivo. Lp(a) but not LDL preferentially induced CD80+ macrophage (M1) polarization and reduced the inducible nitric oxide synthase expression and the subsequent NO production. While shRNA-mediated loss of α7-nAChR function reduced the Lp(a)-induced CD80+ macrophage pool, both shRNA and anti-IL-6 receptor tocilizumab suppressed Lp(a)-upregulated α7-nAChR, p-p38 MAPK, IL-6, and RhoA-GTP protein expression levels in cultures of patient monocyte-derived macrophages and HCASMCs. CONCLUSIONS: Elevated Lp(a) levels upregulate α7-nAChR/IL-6/p38 MAPK signaling in macrophages of CAS patients and HCASMC, suggesting that Lp(a)-triggered inflammation mediates CAS through α7-nAChR/p38 MAPK/IL-6/RhoA-GTP signaling induction, macrophage M1 polarization, and HCASMC activation.

Ptychographic sensor for large-scale lensless microbial monitoring with high spatiotemporal resolution.

Traditional microbial detection methods often rely on the overall property of microbial cultures and cannot resolve individual growth event at high spatiotemporal resolution. As a result, they require bacteria to grow to confluence and then interpret the results. Here, we demonstrate the application of an integrated ptychographic sensor for lensless cytometric analysis of microbial cultures over a large scale and with high spatiotemporal resolution. The reported device can be placed within a regular incubator or used as a standalone incubating unit for long-term microbial monitoring. For longitudinal study where massive data are acquired at sequential time points, we report a new temporal-similarity constraint to increase the temporal resolution of ptychographic reconstruction by 7-fold. With this strategy, the reported device achieves a centimeter-scale field of view, a half-pitch spatial resolution of 488 nm, and a temporal resolution of 15-s intervals. For the first time, we report the direct observation of bacterial growth in a 15-s interval by tracking the phase wraps of the recovered images, with high phase sensitivity like that in interferometric measurements. We also characterize cell growth via longitudinal dry mass measurement and perform rapid bacterial detection at low concentrations. For drug-screening application, we demonstrate proof-of-concept antibiotic susceptibility testing and perform single-cell analysis of antibiotic-induced filamentation. The combination of high phase sensitivity, high spatiotemporal resolution, and large field of view is unique among existing microscopy techniques. As a quantitative and miniaturized platform, it can improve studies with microorganisms and other biospecimens at resource-limited settings.