A case report of recurrent spontaneous coronary artery dissection and Takotsubo cardiomyopathy: a treatment dilemma

Background: Spontaneous coronary artery dissection (SCAD) is an uncommon cause of acute coronary syndrome in younger females with no pre-existing history of coronary artery disease. Recurrent SCAD is common after a first episode and can involve the same coronary artery or present as a new dissection unrelated to the initial lesion. Current recommendations advise for a conservative approach in the absence of haemodynamic compromise and flow limitations. Conversely, there are no clear guidelines for the management of early recurrent SCAD. Case summary: A 52-year-old woman with history of obesity, asthma, and prediabetes presented with chest pain and electrocardiogram (ECG) showing inferior wall ST-elevation myocardial infarction (STEMI). Coronary angiography revealed proximal right coronary artery (RCA) dissection and distal left anterior descending artery (LAD) dissection, while left ventriculogram showed Takotsubo cardiomyopathy (TC). Angiography revealed no flow limitations so conservative management was pursued. She returned within a couple of days with recurrent chest pain and ECG showing similar findings of inferior STEMI. Repeat angiography confirmed progression of the proximal RCA SCAD with resolution of distal LAD SCAD. Since flow through the distal RCA was still preserved, conservative medical management was continued. She presented a third time for palpitations only and another repeat coronary angiogram showed healing RCA SCAD. Discussion: Management of early recurrent SCAD continues to be a clinical dilemma. In addition, our patient had features of TC which shares a similar clinical risk factor profile with SCAD thus it may be prudent to further investigate for TC in patients presenting with SCAD and have suggestive features of TC on history and echocardiography

Exploring metabolic consequences of CPS1 and CAD dysregulation in hepatocellular carcinoma by network reconstruction

Purpose: Hepatocellular carcinoma (HCC) is the fourth commonest cause of cancer-related mortality; it is associated with various genetic alterations, some involved in metabolic reprogramming. This study aimed to explore the potential metabolic impact of Carbamoyl Phosphate Synthase I (CPS1) and carbamoyl phosphate synthetase/aspartate transcarbamoylase/dihydroorotase (CAD) dysregulation through the reconstruction of a network that integrates information from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Human Metabolome Database (HMDB) and Human Protein Atlas (HPA). Methods and Results: Existing literature was used to determine the roles of CPS1 and CAD in HCC. CPS1 downregulation is thought to play a role in hepatocarcinogenesis through an increased glutamine availability for de novo pyrimidine biosynthesis, which CAD catalyzes the first three steps for. KEGG, HMDB and HPA were used to reconstruct a network of relevant pathways, demonstrating the relationships between genes and metabolites using the MetaboSignal package in R. The network was filtered to exclude any duplicates, and those greater than three steps away from CPS1 or CAD. Consequently, a network of 18 metabolites, 28 metabolic genes and 1 signaling gene was obtained, which indicated expression profiles and prognostic information of each gene in the network. Conclusion: Information from different databases was collated to form an informative network that integrated different ‘-omics’ approaches, demonstrating the relationships between genetic and metabolic components of urea cycle and the de novo pyrimidine biosynthesis pathway. This study paves the way for further research by acting as a template to investigate the relationships between genes and metabolites, explore their potential roles in various diseases and aid the development of new screening and treatment methods through network reconstruction

Cell Partitioning Antenna System Performance in Multi-User Scenarios for mmWave Communications

Fixed-beam, high-gain antenna systems can be used for a finer partitioning of the currently used cell-sectoring. This partitioning has the benefit of reducing the number of users seen per antenna beam, which reduces interference. Furthermore, the high antenna gain allows for a high effective isotropic radiated power while keeping the transmit power low. In this paper, we study the performance of such a fixed-beam, high gain antenna system design for millimeter-wave mobile communications. The antenna system is designed to keep the inter-sector interference in a multi-site scenario low. The performance is analyzed for single- and multi-user environments. In single-input single-output mode, the 50th percentile of the signal-to-interference-plus-noise ratio lies between 12.5 dB to 39.7 dB if 3 to 0 interferers are present, respectively. For multiple-input multiple-output transmission using zero-forcing, the signal-to-interference-plus-noise ratio increases and the 50th percentile ranges from 36.1 dB to 43.3 dB if 3 to 0 interferes are present, respectively. By using maximum ratio transmission, the best performance is achieved with no interferers present, while a plunge in performance is observed with interferers. Furthermore, the study revealed that the narrow beam antenna system can also provide a clear signal separation for small spatial separations. In the given example, the signal-to-interference-plus-noise ratio is larger than 32.1 dB with 11 active antenna elements, where 2.8 meters separate the users. Hence, the paper shows that the cell-partitioning antenna systems provide coverage in the desired area while keeping the inter-sector interference low, and the considered transmission techniques can be used for situation optimized mobile communication links

Evidence that Differences in Fructosamine-3-Kinase Activity May be Associated with the Glycation Gap in Human Diabetes

The phenomenon of a discrepancy between glycated haemoglobin levels and other indicators of average glycaemia may be due to many factors but can be measured as the glycation gap (GGap). This GGap is associated with differences in complications in patients with diabetes and may possibly be explained by dissimilarities in deglycation in turn leading to altered production of Advanced Glycation End (AGE) products. We hypothesised that variations in the level of the deglycating enzyme Fructosamine-3-kinase (FN3K) might be associated with the GGap. We measured erythrocyte FN3K concentrations and enzyme activity in a population dichotomised for a large positive or negative GGap. FN3K protein was higher and we found a striking 3-fold greater activity (323%) at any given FN3K protein level in the erythrocytes of the negative compared with positive GGap groups. This was associated with lower AGE levels in the negative GGap group (79%), lower pro-inflammatory adipokines (Leptin/Adiponectin ratio) (73%) and much lower pro-thrombotic PAI-1 levels (19%). We conclude that FN3K may play a key role in the GGap and thus diabetes complications such that FN3K may be potential predictor of the risk of diabetes complications. Pharmacological modifications of its activity may provide a novel approach to their prevention

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan

INTRODUCTION: Although breast carcinoma (BC) is the most common malignancy affecting Jordanian females and the affected population in Jordan is younger than that in the West, no information is available on its biological characteristics. Our aims in this study are to evaluate the expression of estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu overexpression in BC in Jordan, and to compare the expression of these with other prognostic parameters for BC such as histological type, histological grade, tumor size, patients' age, and number of lymph node metastases. METHOD: This is a retrospective study conducted in the Department of Pathology at Jordan University of Science and Technology. A confirmed 91 cases of BC diagnosed in the period 1995 to 1998 were reviewed and graded. We used immunohistochemistry to evaluate the expression of ER, PR, and Her-2. Immunohistochemical findings were correlated with age, tumor size, grade and axillary lymph node status. RESULTS: Her-2 was overexpressed in 24% of the cases. The mean age of Her-2 positive cases was 42 years as opposed to 53 years among Her-2 negative cases (p = 0.0001). Her-2 expression was inversely related to ER and PR expression. Her-2 positive tumors tended to be larger than Her-2 negative tumors with 35% overexpression among T3 tumors as opposed to 22% among T2 tumors (p = 0.13). Her-2 positive cases tended to have higher rates of axillary metastases, but this did not reach statistical significance. ER and PR positive cases were seen in older patients with smaller tumor sizes. CONCLUSION: Her-2 overexpression was seen in 24% of BC affecting Jordanian females. Her-2 overexpression was associated with young age at presentation, larger tumor size, and was inversely related to ER and PR expression. One-fifth of the carcinomas were Her-2 positive and ER negative. This group appears to represent an aggressive form of BC presenting at a young age with large primary tumors and a high rate of four or more axillary lymph node metastases

Peristaltic particle transport using the Lattice Boltzmann method

Peristaltic transport refers to a class of internal fluid flows where the periodic deformation of flexible containing walls elicits a non-negligible fluid motion. It is a mechanism used to transport fluid and immersed solid particles in a tube or channel when it is ineffective or impossible to impose a favorable pressure gradient or desirous to avoid contact between the transported mixture and mechanical moving parts. Peristaltic transport occurs in many physiological situations and has myriad industrial applications. We focus our study on the peristaltic transport of a macroscopic particle in a two-dimensional channel using the lattice Boltzmann method. We systematically investigate the effect of variation of the relevant dimensionless parameters of the system on the particle transport. We find, among other results, a case where an increase in Reynolds number can actually lead to a slight increase in particle transport, and a case where, as the wall deformation increases, the motion of the particle becomes non-negative only. We examine the particle behavior when the system exhibits the peculiar phenomenon of fluid trapping. Under these circumstances, the particle may itself become trapped where it is subsequently transported at the wave speed, which is the maximum possible transport in the absence of a favorable pressure gradient. Finally, we analyze how the particle presence affects stress, pressure, and dissipation in the fluid in hopes of determining preferred working conditions for peristaltic transport of shear-sensitive particles. We find that the levels of shear stress are most hazardous near the throat of the channel. We advise that shear-sensitive particles should be transported under conditions where trapping occurs as the particle is typically situated in a region of innocuous shear stress levels

Operational experience with the GEM detector assembly lines for the CMS forward muon upgrade

The CMS Collaboration has been developing large-area triple-gas electron multiplier (GEM) detectors to be installed in the muon Endcap regions of the CMS experiment in 2019 to maintain forward muon trigger and tracking performance at the High-Luminosity upgrade of the Large Hadron Collider (LHC); 10 preproduction detectors were built at CERN to commission the first assembly line and the quality controls (QCs). These were installed in the CMS detector in early 2017 and participated in the 2017 LHC run. The collaboration has prepared several additional assembly and QC lines for distributed mass production of 160 GEM detectors at various sites worldwide. In 2017, these additional production sites have optimized construction techniques and QC procedures and validated them against common specifications by constructing additional preproduction detectors. Using the specific experience from one production site as an example, we discuss how the QCs make use of independent hardware and trained personnel to ensure fast and reliable production. Preliminary results on the construction status of CMS GEM detectors are presented with details of the assembly sites involvement

The Role of Multiparametric MRI and MRI-targeted Biopsy in the Diagnosis of Radiorecurrent Prostate Cancer: An Analysis from the FORECAST Trial

BACKGROUND: The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear. OBJECTIVE: To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation. DESIGN, SETTING, AND PARTICIPANTS: FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here. INTERVENTION: All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease. RESULTS AND LIMITATIONS: Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation. CONCLUSIONS: For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease. PATIENT SUMMARY: After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed