Genetic tapestry of Capsicum fruit colors: a comparative analysis of four cultivated species.

KEY MESSAGE: Genome-wide association study of color spaces across the four cultivated Capsicum spp. revealed a shared set of genes influencing fruit color, suggesting mechanisms and pathways across Capsicum species are conserved during the speciation. Notably, Cytochrome P450 of the carotenoid pathway, MYB transcription factor, and pentatricopeptide repeat-containing protein are the major genes responsible for fruit color variation across the Capsicum species. Peppers (Capsicum spp.) rank among the most widely consumed spices globally. Fruit color, serving as a determinant for use in food colorants and cosmeceuticals and an indicator of nutritional contents, significantly influences market quality and price. Cultivated Capsicum species display extensive phenotypic diversity, especially in fruit coloration. Our study leveraged the genetic variance within four Capsicum species (Capsicum baccatum, Capsicum chinense, Capsicum frutescens, and Capsicum annuum) to elucidate the genetic mechanisms driving color variation in peppers and related Solanaceae species. We analyzed color metrics and chromatic attributes (Red, Green, Blue, L*, a*, b*, Luminosity, Hue, and Chroma) on samples cultivated over six years (2015-2021). We resolved genomic regions associated with fruit color diversity through the sets of SNPs obtained from Genotyping by Sequencing (GBS) and genome-wide association study (GWAS) with a Multi-Locus Mixed Linear Model (MLMM). Significant SNPs with FDR correction were identified, within the Cytochrome P450, MYB-related genes, Pentatricopeptide repeat proteins, and ABC transporter family were the most common among the four species, indicating comparative evolution of fruit colors. We further validated the role of a pentatricopeptide repeat-containing protein (Chr01:31,205,460) and a cytochrome P450 enzyme (Chr08:45,351,919) via competitive allele-specific PCR (KASP) genotyping. Our findings advance the understanding of the genetic underpinnings of Capsicum fruit coloration, with developed KASP assays holding potential for applications in crop breeding and aligning with consumer preferences. This study provides a cornerstone for future research into exploiting Capsicum's diverse fruit color variation.

Clinical Utility of Soluble Lectin Type Oxidized Low-Density Lipoprotein Receptor as a Biomarker for Myocardial Infarction and Stable Angina.

Background and objectives Endothelial soluble lectin-type oxidized low-density lipoprotein receptor 1 (sLOX-1) recognizes oxidized low-density lipoprotein (LDL) and triggers downstream signaling leading to atherosclerosis. The objective of this study was to demonstrate the utility of sLOX-1 as a biomarker for detecting acute myocardial infarction (MI) and stable angina (SA) and to develop a diagnostic algorithm for distinguishing coronary vasospasm from coronary plaque rupture. Methods We enrolled 62 patients who underwent diagnostic coronary angiography (CAG) and 30 healthy controls (21 men and nine women) and measured sLOX-1, troponin I, and cardiac myosin-binding protein C (c-MyBPC) using commercial kits. Results Patients with MI exhibited higher sLOX-1 levels (301.55 ± 196.16 pg/ml) than patients with stable angina (220.76 ± 103.65 pg/ml) and healthy controls (121.14 ± 77.10, F: 10.55, p<0.001). Although higher troponin I levels were detected in MI patients (263.00 ± 493.00 vs. 3.19 ± 2.15 ng/ml, p=0.0019), no significant elevation was observed in SA patients (1.91 ± 0.79 ng/ml). Plasma sLOX-1 levels showed a positive association with age (r=0.37, p=0.003), but not with gender (r=0.04, p=0.75). Troponin I showed no association with age (r=0.12, p=0.36) or gender (r=0.06, p=0.62). Receiver operating characteristic (ROC) curves revealed that among the three biomarkers, troponin-I showed a higher area under the curve (AUC) (AUC: 0.941), followed by sLOX-1 (AUC: 0.888), while c-MyBPC showed no clinical utility in the detection of MI (AUC: 0.666). Conclusions A marked elevation of sLOX-1 can detect MI and differentiate the presence or absence of plaque rupture, along with diagnosing stable angina.

Transcatheter aortic valve replacement ­ 10 years experience at Gottsegen György National Cardiovascular Center in Hungary / Tíz év tapasztalatai a transzkatéteres aortamubillentyu-implantációval a Gottsegen György Országos Kardiovaszkuláris Intézetben.

Összefoglaló. Bevezetés: A transzkatéteres aortamubillentyu-beültetés (TAVI) az idos, súlyos aortastenosisban szenvedo, multimorbid, magas mutéti kockázattal rendelkezo betegek esetében javasolt a szívsebészeti aortamubillentyu-beültetés alternatívájaként. Célkituzés: Jelen munkánkban az intézetünkben elindult TAVI-program elso 10 éve alatt elvégzett 463, TAVI-n átesett beteg rövid és hosszú távú eredményeit tekintjük át és értékeljük. Külön vizsgáljuk az elso 200 beteg és az utánuk következo 263 beteg eredményeit. Módszer: 2008. november 11. és 2018. december 31. között 463 betegnél végeztünk TAVI-t. Betegeink átlagéletkora 79,6 év, átlagos logisztikus EuroSCORE-értékük 19,0%, átlagos STS-score-értékük pedig 5,2% volt. A beavatkozás elott az esetek 72%-ában NYHA III-as vagy IV-es funkcionális stádiumban voltak. A beavatkozások 92,8%-át transfemoralis behatolásból végeztük. Az aortabillentyun mért átlagos gradiens 50 Hgmm, a billentyuarea 0,55 cm2 volt. Az esetek mintegy 2%-ában az aortabillentyu-bioprotézis restenosisa miatt "valve-in-valve" beavatkozást végeztünk. Eredmények: A TAVI után a 30 napos halálozás 5,2%, az 1 éves pedig 16,4% volt. A TAVI-t követoen kialakult szövodményeket a VARC-2 kritériumrendszere alapján értékeltük. A beavatkozás után 2,2%-ban fordult elo major stroke. A leggyakoribb szövodmény, a posztoperatív pacemakerimplantáció (19,9%) aránya szignifikánsan csökkent a késobb TAVI-n átesett 263 beteg esetében (26,5% vs. 14,8% [p = 0,002]). A vérzéses szövodmények aránya a percutan beavatkozások bevezetésével szignifikánsan emelkedett ugyan (10% vs. 20,2% [p = 0,016]), de ez nem járt a mortalitás emelkedésével. Következtetés: Az eredmények alapján elmondhatjuk, hogy a TAVI intézetünkben is biztonságos alternatívát jelent a magas mutéti rizikóval rendelkezo, súlyos, tünetes aortastenosisban szenvedo betegek esetében. Orv Hetil. 2022; 163(6): 229-235. INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is an alternative treatment to surgical aortic valve replacement for elderly, high surgical risk patients. OBJECTIVE: The aim of this study was to evaluate the short- and long-term outcomes of those 463 patients who underwent TAVI during the first 10 years in our TAVI program. We compare the first 200 patients' results with the further 263 patients' results. METHOD: Between 11th November 2008 and 31st December 2018, 463 patients underwent TAVI. The average age of the patients was 79.6 years, the average logistic EuroSCORE was 19.0%, the average STS score was 5.2%. 72% of the patients were in NYHA III or IV stage before TAVI. 92% of TAVIs were performed from femoral arteries. Average mean gradient was 50.0 mmHg and aortic valve area was 0.55 cm2, respectively. In 2% of the cases, "valve-in-valve" intervention was performed because of the restenosis of former aortic valve prosthesis. RESULTS: 30-day mortality was 5.2% and the 1-year mortality was 16.4% after TAVI. Post-TAVI complications were evaluated according to the VARC-2 definitions. Major stroke occurred in 2.2% after TAVI. The most common complication was pacemaker implantation (19.9%), but their incidence was significantly reduced between the 2 groups (26.5% vs. 14.8% [p = 0.002]). The incidence of vascular access site complications was significantly higher between the 2 groups (10% vs. 20.2% [p = 0.016]), but it did not affect the mortality. CONCLUSION: Based on our results, TAVI is a safe alternative treatment for patients with severe, symptomatic aortic stenosis in our institute as well. Orv Hetil. 2022; 163(6): 229-235.

Association of Promoter Methylation and Expression of Inflammatory Genes IL-6 and TNF-α with the Risk of Coronary Artery Disease in Diabetic and Obese Subjects among Asian Indians.

The inflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) are considered as the most important contributors to the endothelial dysfunction in subjects with type 2 diabetes mellitus (T2DM) and obesity. The hypomethylation of CpG sites in the promoter region of the IL-6 and TNF-α have shown to be associated with the increased expression of IL-6 and TNF-α. However, there are no studies on the methylation and expression of IL-6 and TNF-α with the risk of coronary artery disease (CAD) in subjects with T2DM and obesity in Asian Indians. Hence, the present study was aimed to investigate whether the IL-6, TNF-α promoter methylation and expression in blood leukocyte DNA is associated with the risk of CAD in diabetic and obese subjects in Asian Indians. For this study, we recruited 574 subjects which includes, 207 angiographically confirmed CAD patients, 100 T2DM patients, 82 obese subjects and 185 healthy controls. The methylation status of IL-6 and TNF-α gene loci was determined by methylation specific PCR (MPCR) and gene expression was determined by qPCR. We found significant hypomethylation of IL-6 in CAD and T2DM subjects (OR 1.98 95% CI: 1.32-2.97, p = 0.001, OR: 2.23 95% CI:1.34-3.76, p = 0.001, respectively). Further, a significant increase in the expression of IL-6 in CAD and T2DM subjects (fold change: 26.39 & 14.7, p = 0.0001) compared to the control subjects was observed. A significant increase in the hypomethylation of TNF-α in CAD, T2DM and obese subjects was observed as compared to the control (OR: 2.04 95% CI: 1.36-3.05, p = 0.0005, OR: 1.81 95% CI 1.10-2.96, p = 0.01, and OR: 2.1 95% CI 1.24-3.57, p = 0.007, respectively).We also found an increased expression of TNF-α in CAD, T2DM and obese subjects as compared to controls. In addition, presence of low folate, and hyperhomocysteinemia was observed in the present study, may be the contributing factors for the hypomethylation of IL-6 and TNF-α and oxidative stress. In conclusion, increased expression of IL-6 and TNF-α due to hypomethylation in T2DM and obese individuals may contribute to CAD risk in these subjects. The presence of hyperhomocysteinemia and increased oxidative risk may enhance the CAD risk further.

Relationship of echocardiographic left ventricular dyssynchrony with QRS width on surface electrocardiogram in patients with systolic heart failure: An observational study.

This study aimed to evaluate left ventricular dyssynchrony with QRS width on ECG in patients with systolic heart failure. 100 study patients were classified into two groups. Narrow QRS group-N- QRS (80-119 msec) and Wide QRS group-W- QRS (120-160 msec). Out of each 50 patients in W- QRS group, 38(76%) had LV dyssynchrony and 18 (36%) in N- QRS group had ventricular dyssynchrony. Dyssynchrony in narrow QRS patients with heart failure also needs attention as a therapeutic target in future studies.

Multipronged approach to a patient with ventricular tachycardia storm.

Management of ventricular tachycardia storm requires multimodal aggressive therapeutic interventions for a successful outcome. A 39-year-old man with dilated cardiomyopathy and severe left ventricular dysfunction presented with refractory ventricular tachycardia unresponsive to conventional treatment. He underwent an electrophysiology study and radiofrequency ablation with 3-dimensional mapping with partial control of the ventricular tachycardia. Further left sympathetic ganglion block followed by left cardiac sympathetic denervation also did not totally control the ventricular tachycardia. Right cardiac sympathetic denervation resulting in bilateral cardiac sympathetic denervation controlled the ventricular tachycardia.

Probing the epigenetic signatures in subjects with coronary artery disease.

Depletion of S-adenosyl methionine and 5-methyltetrahydrofolate; and elevation of total plasma homocysteine were documented in CAD patients, which might modulate the gene-specific methylation status and alter their expression. In this study, we have aimed to delineate CAD-specific epigenetic signatures by investigating the methylation and expression of 11 candidate genes i.e. ABCG1, LIPC, PLTP, IL-6, TNF-α, CDKN2A, CDKN2B, F2RL3, FGF2, P66 and TGFBR3. The methylation-specific PCR and qRT-PCR were used to assess the methylation status and the expression of candidate genes, respectively. CAD patients showed the upregulation of IL-6, TNF-α, CDKN2A, CDKN2B, F2RL3, FGF2, P66, and TGFBR3. Hypomethylation of CDKN2A loci was shown to increase risk for CAD by 1.79-folds (95% CI 1.22-2.63). Classification and regression tree (CART) model of gene expression showed increased risk for CAD with F2RL3 > 3.4-fold, while demonstrating risk reduction with F2RL3 < 3.4-fold and IL-6 < 7.7-folds. This CAD prediction model showed the excellent sensitivity (0.98, 95% CI 0.88-1.00), specificity (0.91, 95% CI 0.86-0.92), positive predictive value (0.82, 95% CI 0.75-0.84), and negative predictive value (0.99, 95% CI 0.94-1.00) with an overall accuracy of 92.8% (95% CI 87.0-94.1%). Folate and B12 deficiencies were observed in CAD cases, which were shown to contribute to hypomethylation and upregulation of the prime candidate genes i.e. CDKN2A and F2RL3. Early onset diabetes was associated with IL-6 and TNF-α hypomethylation and upregulation of CDKN2A. The expression of F2RL3 and IL-6 (or) hypomethylation status at CDKN2A locus are potential biomarkers in CAD risk prediction. Early epigenetic imprints of CAD were observed in early onset diabetes. Folate and B12 deficiencies are the contributing factors to these changes in CAD-specific epigenetic signatures.

Women with drug-resistant epilepsy: Surgery or pregnancy first?

OBJECTIVE: We compared women with drug-resistant focal epilepsy who had undergone surgery (WWE-S) with those who were managed medically (WWE-M) for maternal and fetal outcomes of their pregnancies. METHODS: We classified all WWE-S who were enrolled in a prospective registry of epilepsy and pregnancy (1998-2015) as those who underwent the surgery before pregnancy (WWE-SF) or after pregnancy (WWE-PF). The comparator group (WWE-M) was twice that number of age-matched women with focal epilepsy in this registry. Their clinical profile, anti-epileptic drug (AED) use, and pregnancy outcomes were extracted from the records of the registry. RESULTS: The number of completed pregnancies with known outcome was 74 for WWE-S (67 WWE-SF and 7 WWE-PF) and 134 for WWE-M. Seizures increased during pregnancy for fewer WWE-SF than for WWE-M (14.9% vs 39.6%, P = .001). Compared to WWE-M, fewer WWE-SF had dose escalation during pregnancy (28.4% vs 14.9%, P = .025). Preterm deliveries were more frequent in WWE-SF than WWE-M (24.6% vs 12.2%, P = .029). The differences between the WWE-SF and WWE-M regarding the rates of fetal loss (10.4% vs 6.7%, P = .255), major congenital malformations (8.5% vs. 11.1%, P = .395), and development quotient at 1 year of age <85 (42.5% vs 42.3%, P = .569) were not statistically significant. Compared to WWE-PF, fewer WWE-SF had AED dose escalation (14.9% vs 85.7%, P = .001) or increase in seizures (14.9% vs 100%, P = .001) during pregnancy. WWE-SF had fewer infants with development quotient <85 (41.0% vs 100%, P = .005). SIGNIFICANCE: WWE-SF can expect better control of seizures and decreased AED burden during pregnancy than WWE with focal epilepsies managed with medicines only. WWE who undergo surgery for epilepsy before their pregnancies can expect fewer seizures and lower AED burden during pregnancy.

A Prospective Study on Prevalence and Causes of Anaemia in Patients with Acute Coronary Syndrome.

INTRODUCTION: Anaemia is a contributor for adverse prognosis in Acute Coronary Syndrome (ACS), but the epidemiology and causes of anaemia in such patients is not defined. AIM: To study the prevalence and aetiology of anaemia in hospitalized patients with ACS. MATERIALS AND METHODS: All consecutive patients admitted with ACS from January to March, 2010 were included. Their clinical information was recorded. RESULTS: Of 130 (87 males) consecutive admissions for ACS, 47.7% had unstable angina, 10% had Non ST-Elevation Myocardial Infarction (NSTEMI) and 42.3% had ST-Elevation Myocardial Infarction (STEMI). Overall prevalence of anaemia (haemoglobin <130 g/l in men and <120 g/l in women) was 51.5% (n=67) and was more prevalent in women (n=30, 69.8%) than men (n=37, 42.5%). Moderate to severe anaemia was more in women (34.9%) compared to men (20.8%). Anaemia was more common in unstable angina patients (58.2%) than in NSTEMI (11.9%) or STEMI (29.9%) patients (p=0.013). Aspirin (p<0.01) and/or clopidogrel intake (p<0.01) and raised serum creatinine (p<0.01) were more often in anaemic patients. Heart failure (p<0.01) and triple vessel disease (p<0.05) were associated with anaemia. Multivariate predictors of duration of hospital stay were haemoglobin (p<0.05) at admission and revascularisation procedure (p=0.01) during hospital stay. The most common cause of anaemia was iron deficiency (29.9%). CONCLUSION: Anaemia was common in our patients admitted with ACS. Female gender, antiplatelet drug intake and raised creatinine were associated with anaemia, which in turn was associated with adverse in-hospital outcomes. The impact of correcting anaemia on outcomes in ACS needs long term prospective study.

Adrenal and extra-adrenal pheochromocytomas presenting as life-threatening ventricular arrhythmias: Report of three cases.

Pheochromocytoma patients can rarely have prolonged QT interval in the ECG. We report three cases of pheochromocytoma in females presenting with ventricular arrhythmia; two had torsades de pointes and a third patient had frequent VPCs and nonsustained ventricular tachycardia. All the patients were treated with surgical removal of the tumor with complete relief of symptoms and normalization of QT interval.

Clinical picture of arrhythmogenic right ventricular dysplasia / cardiomyopathy patients from Indian origin.

OBJECTIVE: Among the inherited cardiomyopathies, Arrhythmogenic right ventricular dysplasia/cardiomyopathy is unique with a peculiar pathology of fibro-fatty replacement. Studies have been carried out all over the world and several groups have reported clinical heterogeneity in manifestation of ARVD/C related symptoms. Present study is an attempt to identify the clinical profile of ARVD/C patients from Asian Indian origin. METHODS: 31 patients in the span of three years were diagnosed with ARVD/C. Diagnosis was based on proposed task force criteria. RESULTS: The mean age at diagnosis was 32.9 +/- 16.4 years with slight tilt in male to female ratio (1.46). About 80% cases had palpitations, syncope in 45.16% and dyspnea in 22.5%, whereas 16% of patients were asymptomatic. About 50% of patients revealed a family history of confirmed ARVD/C or sudden death of a family member without any known cause. ECG showed T-wave inversion in about 60% cases, prolongation of QRS was observed in 20% cases. RV dilatation was observed in 80% of patients and 66.7% showed systolic dysfunction. RV free wall motion abnormalities were found in 33% patients. Most of the early onset cases with less than 30 years of age showed family history indicative of ARVD/C. Familial study in three patients indicated early onset of condition in younger generations in two families. CONCLUSIONS: ARVD/C in India shows relatively early age at onset when compared with other Asian populations with more than half of patients showing the disease below the age of 30 years. History in most of the early onset cases revealed family history indicating strong genetic influence.