Is there an immunogenomic difference between thoracic and abdominal aortic aneurysms?

BACKGROUND AND AIM: Aortic aneurysms most commonly occur in the infra-renal and proximal thoracic regions. While generally asymptomatic, progressive aneurysmal dilation can become rapidly lethal when dissection or ruptures occurs, highlighting the need for more robust screening. Abdominal aortic aneurysm (AAA) is more prevalent compared to thoracic aortic aneurysm (TAA). The true incidence of TAA is underreported due to the absence of population screening and the silent nature of TAA. To achieve the optimum survival rate in aortic aneurysms, knowledge of natural course, genetic association, and surgical results are needed to be applied with adequate medical treatment and careful selection of patients for operation. The purpose of this paper is to provide a comprehensive review of the literature on natural history, immunology, and genetic differences between thoracic and AAAs. METHOD: The literature was collected from OVID, SCOPUS, and PubMed. RESULTS: (1) AAA expands faster than TAA. AAA expands at approximately 0.3-0.45 cm annually, depending on various factors (advancing age, diameter of aorta, smoking etc.). TAA expands up to 0.3 cm annually in a non-bicuspid aortic valve patient. (2) An increase in Matrix metallopeptidase 1, 2, 9, 12, 14 led to degrading extracellular matrix of the aortic vessel wall. This significantly contributed to the pathogenesis in AAA, whereas overactive Transforming growth factor-beta played a major role in the pathogenesis of TAA. CONCLUSION: In the future, genetic testing may be the gold standard for tackling the geneticheterogeneity of aneurysms, therefore, identifying at-risk individuals developing TAA andAAA earlier.

Tear Size and Location Influence the Pressure of False Lumen Following Type A Aortic Dissection: Perspective of Current Evidence.

Aortic dissection is a surgical emergency which poses a challenge to numerous clinicians across different specialties due to its high rate of associated morbidity and mortalities. Acute type A aortic dissection, which involves the ascending aorta and beyond, is a lethal condition. It is therefore vital to understand the pathophysiology that underlies this condition and the tools that aid its early detection. Haemodynamics factors including lumen wall shear stress and pressure, geometrical factors as entry tear location and size, and the composition of the aortic wall are well known to affect the disease progression. The studies on these factors are well established in Type B aortic dissection but not clearly emphasised in the setting of acute type A aortic dissection. The aim of this paper is to provide a comprehensive review of available literature on the relationship between tear size, location and the pressure of false lumen in acute type A aortic dissection.

Basal Subnuclear Vacuolization, Armanni-Ebstein Lesions, Wischnewsky Lesions, and Elevated Vitreous Glucose and ß-Hydroxybuyrate: Is It Hypothermia, Diabetic Ketoacidosis, or Both?

Hypothermia and diabetic ketoacidosis are both potentially fatal conditions, which have historically been considered to have associated pathognomonic pathologies. Hypothermia and diabetic ketoacidosis share similar pathological mechanisms, which result in metabolic derangement, with increased post mortem vitreous glucose and ß-hydroxybuyrate, and are able to exacerbate and precipitate one another. Although Wischnewsky lesions are associated with hypothermia, and Armanni-Ebstein lesions and basal subnuclear vacuolization are associated with diabetic ketoacidosis, recent studies have demonstrated that there is a significant overlap between the pathological findings of these 2 conditions. We report a case of a 50-year-old woman with type 1 diabetes who was found deceased in the middle of winter. Autopsy showed Wischnewsky lesions, Armanni-Ebstein lesions, and basal subnuclear vacuolization, together with elevated vitreous glucose and ß-hydroxybuyrate. The cause of death was the combined effects of hypothermia and diabetic ketoacidosis. This case highlights the overlapping clinical presentation, pathophysiology, and pathology of these 2 conditions.

A Rare Case of Isolated Atrial Myocarditis Causing Death With no Post Mortem Computed Tomography Scan Correlation.

Acute myocarditis is a potentially fatal cardiac pathology that is thought to cause sudden death through arrhythmia and cardiac failure. Of the different subtypes, lymphocytic myocarditis is the most common form. The pathophysiology of myocarditis can be generally diffuse or focally involve the ventricles, but less frequently affects the atria. Although the clinical literature reports isolated atrial myocarditis as a cause of atrial fibrillation and enlargement, there is scant postmortem literature on the findings of this pathology. We report a fatal case of isolated lymphocytic atrial myocarditis affecting only the left atrium in a 56-year-old man, where microscopy of the left atrium confirmed a florid lymphocytic myocarditis. Retrospective postmortem computed tomography scan review did not show any abnormalities on the left atrial wall.

Evidence of differential selection for the -α(3.7) and -α(4.2) single-α-globin gene deletions within the same population.

Since the 1950s, a strong correlation between high carrier rates for ß-thalassemia mutations and selective survival advantage in tropical and subtropical 'malarial belt' regions has been established. Due to the relatively more complex genetics of α-thalassemia, a similar relationship was demonstrated for α-globin gene mutations only from the 1980s, with both single- and double-α-globin gene deletions prevalent in the malarial belt. Mechanistically, the single-α-globin gene deletions arise from non-allelic recombination between the homologous α1 (HBA1) and α2 (HBA2) globin genes. Compared to the -α(3.7) and ααα(anti3.7) rightward crossover alleles, much less is known about the -α(4.2) and ααα(anti4.2) leftward crossover alleles. We performed a survey of 1,285 unselected cord blood samples from the 3 major ethnic groups in Singapore. Overall, the frequency of the -α(3.7) deletion was significantly higher than its reciprocal ααα(anti3.7) triplication, consistent with positive selection for the -α(3.7) single-gene deletion. In marked contrast, there was no significant difference in frequency between the -α(4.2) and reciprocal ααα(anti4.2) alleles, suggesting the absence of positive selection for the -α(4.2) single-gene deletion. The similar ααα(anti3.7) and ααα(anti4.2) allele frequencies also suggested that the crossover rates at X and Z homology boxes are similar. Taken together, these observations suggest a differential positive selection for the -α(3.7) and -α(4.2) alleles within the same population. Further population and biological studies may be required to explain these current observations.

Anti-Cancer Effects of Epigenetics Drugs Scriptaid and Zebularine in Human Breast Adenocarcinoma Cells.

BACKGROUND: High relapse and metastasis progression in breast cancer patients have prompted the need to explore alternative treatments. Epigenetic therapy has emerged as an attractive therapeutic strategy due to the reversibility of epigenome structures. OBJECTIVE: This study investigated the anti-cancer effects of epigenetic drugs scriptaid and zebularine in human breast adenocarcinoma MDA-MB-231 and MCF-7 cells. METHODS: First, the half maximal Inhibitory Concentration (IC50) of scriptaid and zebularine, and the combination of both drugs on human breast adenocarcinoma MDA-MB-231 cells were determined. Next, MDA-MB-231 and MCF-7 cells were treated with IC50 of scriptaid, zebularine and the combination of both. After IC50 treatments, the anti-cancer effects were evaluated via cell migration assay, cell cycle analysis and apoptotic studies which included histochemical staining and reverse-transcriptase polymerase chain reaction (RT-PCR) of the apoptotic genes. RESULTS: Both epigenetic drugs inhibited cell viability in a dose-dependent manner with IC50 of 2 nM scriptaid, 8 µM zebularine and a combination of 2 nM scriptaid and 2 µM zebularine. Both MDA-MB-231 and MCF-7 cells exhibited a reduction in cell migration after the treatments. In particular, MDA-MB-231 cells exhibited a significant reduction in cell migration (p < 0.05) after the treatments of zebularine and the combination of scriptaid and zebularine. Besides, cell cycle analysis demonstrated that scriptaid and the combination of both drugs could induce cell cycle arrest at the G0/G1 phase in both MDA-MB-231 and MCF-7 cells. Furthermore, histochemical staining allowed the observation of apoptotic features, such as nuclear chromatin condensation, cell shrinkage, membrane blebbing, nuclear chromatin fragmentation and cytoplasmic extension, in both MDA-MB-231 and MCF-7 cells after the treatments. Further, apoptotic studies revealed the upregulation of pro-apoptotic Bax, downregulation of anti-apoptotic Bcl-2 and elevation of Bax/Bcl-2 ratio in MDA-MB-231 cells treated with zebularine and MCF-7 cells treated with all drug regimens. CONCLUSION: Collectively, these findings suggest that scriptaid and zebularine are potential anti-cancer drugs, either single or in combination, for the therapy of breast cancer. Further investigations of the gene regulatory pathways directed by scriptaid and zebularine are definitely warranted in the future.

Evaluation of the performance of Torulaspora delbrueckii, Williopsis saturnus, and Kluyveromyces lactis in lychee wine fermentation.

This study evaluated the effects of three non-Saccharomyces yeasts, namely Torulaspora delbrueckii PRELUDE, Williopsis saturnus NCYC22, and Kluyveromyces lactis KL71 on lychee juice fermentation. The fermentation performance of these non-Saccharomyces yeasts was significantly different. T. delbrueckii PRELUDE had the fastest rate of growth and high sugar consumption. W. saturnus NCYC22 used the lowest amount of sugars, but consumed the highest amount of nitrogen. Correspondingly, strain PRELUDE produced the highest level of ethanol (7.6% v/v), followed by strain KL71 (3.4% v/v) and strain NCYC22 (0.8% v/v). Aroma character-impact terpenes and terpenoids could be partially retained in all lychee wines, with higher odour activity values (OAVs) of geraniol and citronellol in strain KL71. However, strain KL71 and strain NCYC22 over-produced ethyl acetate. Strain PRELUDE had a better ability to generate high levels of ethanol, isoamyl alcohol, 2-phenylethyl alcohol, ethyl octanoate, and ethyl decanoate and retained high OAVs of lychee aroma-character compounds cis-rose oxide (16.5) and linalool (3.5). Thus, it is deemed to be a promising non-Saccharomyces yeast for lychee wine fermentation.

TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport.

The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions.