Cryoballoon cardioneuroablation: New electrophysiological insights.

Background: Cardioneuroablation (CNA) targeting ganglionated plexi has shown promise in treating vasovagal syncope. Only radiofrequency ablation has been used to achieve this goal thus far. Objective: The purpose of this study was to investigate the utility of cryoballoon ablation (CBA) of the pulmonary veins (PVs) as a potential simplified approach to CNA. Methods: We report our observations of autonomic modulation in a series of 17 patients undergoing CBA for atrial fibrillation and our early experience using CBA of the PVs in 3 patients with malignant vagal syncope. In 17 patients undergoing CBA of AF, sinus cycle length was recorded intraprocedurally after ablation of individual PVs. Results: The most pronounced shortening of the sinus cycle length was observed after isolation of the right upper PV, which was ablated last. Reduced sinus node recovery time and atrioventricular (AV) nodal effective refractory period were observed after CBA. Resting heart rate was elevated by 6-7 bpm after CBA and persisted during 12-month follow-up. CBA of the PVs was performed in 3 patients with recurrent vagal syncope mediated by sinus arrest (n = 2) and AV block (n = 1). In all patients, isolation of the right upper PV resulted in marked shortening of sinus cycle length. During follow-up of 178 ± 43 days (134-219 days), CNA resulted in abolition of pauses, bradycardia-related symptoms, and syncope in all patients. Conclusion: CBA of the PVs (particularly the right upper PV) may be a predictable anatomic CNA approach in patients with refractory vagal syncope due to sinus arrest and/or AV block and may warrant systematic investigation as a tool to perform CNA.

Meta-analysis of identified genomic regions and candidate genes underlying salinity tolerance in rice (Oryza sativa L.).

Rice output has grown globally, yet abiotic factors are still a key cause for worry. Salinity stress seems to have the more impact on crop production out of all abiotic stresses. Currently one of the most significant challenges in paddy breeding for salinity tolerance with the help of QTLs, is to determine the QTLs having the best chance of improving salinity tolerance with the least amount of background noise from the tolerant parent. Minimizing the size of the QTL confidence interval (CI) is essential in order to primarily include the genes responsible for salinity stress tolerance. By considering that, a genome-wide meta-QTL analysis on 768 QTLs from 35 rice populations published from 2001 to 2022 was conducted to identify consensus regions and the candidate genes underlying those regions responsible for the salinity tolerance, as it reduces the confidence interval (CI) to many folds from the initial QTL studies. In the present investigation, a total of 65 MQTLs were extracted with an average CI reduced from 17.35 to 1.66 cM including the smallest of 0.01 cM. Identification of the MQTLs for individual traits and then classifying the target traits into correlated morphological, physiological and biochemical aspects, resulted in more efficient interpretation of the salinity tolerance, identifying the candidate genes and to understand the salinity tolerance mechanism as a whole. The results of this study have a huge potential to improve the rice genotypes for salinity tolerance with the help of MAS and MABC.

Characterization of CcTFL1 Governing Plant Architecture in Pigeon pea (Cajanus cajan (L.) Millsp.).

Growth habits are among the essential adaptive traits acted upon by evolution during plant speciation. They have brought remarkable changes in the morphology and physiology of plants. Inflorescence architecture varies greatly between wild relatives and cultivars of pigeon pea. The present study isolated the CcTFL1 (Terminal Flowering Locus 1) locus using six varieties showing determinate (DT) and indeterminate (IDT) growth habits. Multiple alignments of CcTFL1 sequences revealed the presence of InDel, which describes a 10 bp deletion in DT varieties. At the same time, IDT varieties showed no deletion. InDel altered the translation start point in DT varieties, resulting in the shortening of exon 1. This InDel was validated in ten varieties of cultivated species and three wild relatives differing in growth habits. The predicted protein structure showed the absence of 27 amino acids in DT varieties, which was reflected in mutant CcTFL1 by the absence of two α-helices, a connecting loop, and shortened ß-sheet. By subsequent motif analysis, it was found that the wild-type protein had a phosphorylation site for protein kinase C, but the mutant protein did not. In silico analysis revealed that the InDel-driven deletion of amino acids spans, containing a phosphorylation site for kinase protein, may have resulted in the non-functionality of the CcTFL1 protein, rendering the determinate growth habit. This characterization of the CcTFL1 locus could be used to modulate growth habits through genome editing.

Defining the Middle Corona.

The middle corona, the region roughly spanning heliocentric distances from 1.5 to 6 solar radii, encompasses almost all of the influential physical transitions and processes that govern the behavior of coronal outflow into the heliosphere. The solar wind, eruptions, and flows pass through the region, and they are shaped by it. Importantly, the region also modulates inflow from above that can drive dynamic changes at lower heights in the inner corona. Consequently, the middle corona is essential for comprehensively connecting the corona to the heliosphere and for developing corresponding global models. Nonetheless, because it is challenging to observe, the region has been poorly studied by both major solar remote-sensing and in-situ missions and instruments, extending back to the Solar and Heliospheric Observatory (SOHO) era. Thanks to recent advances in instrumentation, observational processing techniques, and a realization of the importance of the region, interest in the middle corona has increased. Although the region cannot be intrinsically separated from other regions of the solar atmosphere, there has emerged a need to define the region in terms of its location and extension in the solar atmosphere, its composition, the physical transitions that it covers, and the underlying physics believed to shape the region. This article aims to define the middle corona, its physical characteristics, and give an overview of the processes that occur there.

Editor's Choice - Therapeutic Options and Outcomes in Midaortic Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: Midaortic syndrome (MAS) is narrowing of the distal thoracic and or abdominal aorta with congenital, inflammatory, or idiopathic aetiology. If left untreated, the prognosis is poor due to hypertensive complications. Follow up data after treatment are sparse, contrary to aortic coarctation. This study aimed to investigate hypertension during follow up after medical, endovascular, and surgical therapy in juveniles and adults. DATA SOURCES: A meta-analysis of case series and reports was performed, focusing on the incidence of hypertension during the follow up of juvenile (i.e., age 0-17 years) and adult MAS patients after medical, endovascular, or surgical therapy. REVIEW METHODS: Search queries were performed in PubMed, Embase, and Web of Science, and eligible articles underwent quality control. Descriptive statistics were reported based on available data, and individual patient data meta-analyses were performed using a one stage approach, accounting for clustering by case series or decades of reporting for case reports. For the meta-analysis, missing outcome and aetiology data were multiply imputed. RESULTS: The number of juveniles and adults who underwent endovascular therapy (33.7% vs. 27.3%; p = .42) and surgery (52.2% vs. 58.0%; p = .46) was similar. At baseline, 92.4% of juveniles and 87.5% of adults were hypertensive, decreasing to 23.2% and 24.1% during a follow up of 23 months (juveniles) and 18 months (adults), respectively. More hypertension was found compared with surgery in juveniles after endovascular therapy (38.1% vs. 10.8%; p = .020). Meta-analysis also demonstrated a trend for hypertension after endovascular therapy in juveniles, whereas hypertension was more prevalent following surgery in adults compared with endovascular therapy or medication. CONCLUSION: This review and meta-analysis investigated therapeutic options for MAS in juveniles and adults. It found that complications and hypertension during follow up were more common in juveniles after endovascular treatment, whereas surgery in adults was associated with more hypertension.

Relationships Between Atrial Flutter and Fibrillation: The Border Zone.

Atrial flutter and fibrillation have been inextricably linked in the study of electrophysiology. With astute clinical observation, advanced diagnostic equipment in the Electrophysiology Laboratory, and thoughtful study of animal models, the mechanism and inter-relationship between the 2 conditions have been elucidated and will be reviewed in this article. Though diagnosis and management of these conditions have many similarities, the mechanisms by which they develop and persist are quite unique.

Phylogenetic analysis of phytochrome A gene from Lablab purpureus (L.) Sweet.

BACKGROUND: Phytochromes are the best characterized photoreceptors that perceive Red (R)/Far-Red (FR) signals and mediate key developmental responses in plants. It is well established that photoperiodic control of flowering is regulated by PHY A (phytochrome A) gene. So far, the members of PHY A gene family remains unexplored in Lablab purpureus, and therefore, their functions are still not deciphered. PHYA3 is the homologue of phytochrome A and known to be involved in dominant suppression of flowering under long day conditions by downregulating florigens in Glycine max. The present study is the first effort to identify and characterize any photoreceptor gene (PHYA3, in this study) in Lablab purpureus and decipher its phylogeny with related legumes. RESULTS: PHYA3 was amplified in Lablab purpureus cv GNIB-21 (photo-insensitive and determinate) by utilizing primers designed from GmPHYA3 locus of Glycine max. This study was successful in partially characterizing PHYA3 in Lablab purpureus (LprPHYA3) which is 2 kb longer and belongs to exon 1 region of PHYA3 gene. Phylogenetic analysis of the nucleotide and protein sequences of PHYA genes through MEGA X delineated the conservation and evolution of Lablab purpureus PHYA3 (LprPHYA3) probably from PHYA genes of Vigna unguiculata, Glycine max and Vigna angularis. A conserved basic helix-loop-helix motif bHLH69 was predicted having DNA binding property. Domain analysis of GmPHYA protein and predicted partial protein sequence corresponding to exon-1 of LprPHYA3 revealed the presence of conserved domains (GAF and PAS domains) in Lablab purpureus similar to Glycine max. CONCLUSION: Partial characterization of LprPHYA3 would facilitate the identification of complete gene in Lablab purpureus utilizing sequence information from phylogenetically related species of Fabaceae. This would allow screening of allelic variants for LprPHYA3 locus and their role in photoperiod responsive flowering. The present study could aid in modulating photoperiod responsive flowering in Lablab purpureus and other related legumes in near future through genome editing.

Racial and Socioeconomic Disparities in Out-Of-Hospital Cardiac Arrest Outcomes: Artificial Intelligence-Augmented Propensity Score and Geospatial Cohort Analysis of 3,952 Patients.

INTRODUCTION: Social disparities in out-of-hospital cardiac arrest (OHCA) outcomes are preventable, costly, and unjust. We sought to perform the first large artificial intelligence- (AI-) guided statistical and geographic information system (GIS) analysis of a multiyear and multisite cohort for OHCA outcomes (incidence and poor neurological disposition). METHOD: We conducted a retrospective cohort analysis of a prospectively collected multicenter dataset of adult patients who sequentially presented to Houston metro area hospitals from 01/01/07-01/01/16. Then AI-based machine learning (backward propagation neural network) augmented multivariable regression and GIS heat mapping were performed. RESULTS: Of 3,952 OHCA patients across 38 hospitals, African Americans were the most likely to suffer OHCA despite representing a significantly lower percentage of the population (42.6 versus 22.8%; p < 0.001). Compared to Caucasians, they were significantly more likely to have poor neurological disposition (OR 2.21, 95%CI 1.25-3.92; p=0.006) and be discharged to a facility instead of home (OR 1.39, 95%CI 1.05-1.85; p=0.023). Compared to the safety net hospital system primarily serving poorer African Americans, the university hospital serving primarily higher income commercially and Medicare insured patients had the lowest odds of death (OR 0.45, p < 0.001). Each additional $10,000 above median household income was associated with a decrease in the total number of cardiac arrests per zip code by 2.86 (95%CI -4.26- -1.46; p < 0.001); zip codes with a median income above $54,600 versus the federal poverty level had 14.62 fewer arrests (p < 0.001). GIS maps showed convergence of the greater density of poor neurologic outcome cases and greater density of poorer African American residences. CONCLUSION: This large, longitudinal AI-guided analysis statistically and geographically identifies racial and socioeconomic disparities in OHCA outcomes in a way that may allow targeted medical and public health coordinated efforts to improve clinical, cost, and social equity outcomes.

Spectrum and Relevance of Incidental Bowel Findings on Computed Tomography.

A wide spectrum of incidental bowel findings can be seen on CT, including but not limited to, pneumatosis intestinalis, diverticular disease, non-obstructive bowel dilatation, transient small bowel intussusception, and submucosal fat. Radiologists should be aware that such findings are almost always benign and of little clinical significance in the absence of associated symptoms. Conversely, vigilance must be maintained when evaluating the bowel, because malignant neoplasms occasionally come to clinical attention as incidental imaging findings. When suspicious incidental bowel wall thickening is detected, the radiologist can alert the clinical team to the finding prior to the patient becoming symptomatic, potentially leading to definitive management at an early, more curable stage.

Geographical Differences in Cardiovascular Comorbidities and Outcomes of COVID-19 Hospitalized Patients in the USA.

INTRODUCTION: Cardiovascular comorbidities may predispose to adverse outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). However, across the USA, the burden of cardiovascular comorbidities varies significantly. Whether clinical outcomes of hospitalized patients with COVID-19 differ between regions has not yet been studied systematically. Here, we report differences in underlying cardiovascular comorbidities and clinical outcomes of patients hospitalized with COVID-19 in Texas and in New York state. METHODS: We established a multicenter retrospective registry including patients hospitalized with COVID-19 between March 15 and July 12, 2020. Demographic and clinical data were manually retrieved from electronic medical records. We focused on the following outcomes: mortality, need for pharmacologic circulatory support, need for mechanical ventilation, and need for hemodialysis. Univariate and multivariate logistic regression analyses were performed. RESULTS: Patients in the Texas cohort (n = 296) were younger (57 vs. 63 years, p value <0.001), they had a higher BMI (30.3 kg/m2 vs. 28.5 kg/m2, p = 0.015), and they had higher rates of diabetes mellitus (41 vs. 30%; p = 0.014). In contrast, patients in the New York state cohort (n = 218) had higher rates of coronary artery disease (19 vs. 10%, p = 0.005) and atrial fibrillation (11 vs. 5%, p = 0.012). Pharmacologic circulatory support, mechanical ventilation, and hemodialysis were more frequent in the Texas cohort (21 vs. 13%, p = 0.020; 30 vs. 12%, p < 0.001; and 11 vs. 5%, p = 0.009, respectively). In-hospital mortality was similar between the 2 cohorts (16 vs. 18%, p = 0.469). After adjusting for differences in underlying comorbidities, only the use of mechanical ventilation remained significantly higher in the participating Texas hospitals (odds ratios [95% CI]: 3.88 [1.23, 12.24]). Median time to pharmacologic circulatory support was 8 days (interquartile range: 2, 13.8) in the Texas cohort compared to 1 day (0, 3) in the New York state cohort, while median time to in-hospital mortality was 16 days (10, 25.5) and 7 days (4, 14), respectively (both p < 0.001). In-hospital mortality was higher in the late versus the early study phase in the New York state cohort (24 vs. 14%, p = 0.050), while it was similar between the 2 phases in the Texas cohort (16 vs. 15%, p = 0.741). CONCLUSIONS: Geographical differences, including practice pattern variations and the impact of disease burden on provision of health care, are important for the evaluation of COVID-19 outcomes. Unadjusted data may cause bias affecting future regulatory policies and proper allocation of resources.

Allelic characterization and protein structure analysis reveals the involvement of splice site mutation for growth habit differences in Lablab purpureus (L.) Sweet.

BACKGROUND: Interrelationship between growth habit and flowering played a key role in the domestication history of pulses; however, the actual genes responsible for these traits have not been identified in Indian bean. Determinate growth habit is desirable due to its early flowering, photo-insensitivity, synchronous pod maturity, ease in manual harvesting and short crop duration. The present study aimed to identify, characterize and validate the gene responsible for growth habit by using a candidate gene approach coupled with sequencing, multiple sequence alignment, protein structure prediction and binding pocket analysis. RESULTS: Terminal flowering locus was amplified from GPKH 120 (indeterminate) and GNIB-21 (determinate) using the primers designed from PvTFL1y locus of common bean. Gene prediction revealed that the length of the third and fourth exons differed between the two alleles. Allelic sequence comparison indicated a transition from guanine to adenine at the end of the third exon in GNIB 21. This splice site single-nucleotide polymorphism (SNP) was validated in germplasm lines by sequencing. Protein structure analysis indicated involvement of two binding pockets for interaction of terminal flowering locus (TFL) protein with other proteins. CONCLUSION: The splice site SNP present at the end of the third exon of TFL locus is responsible for the transformation of shoot apical meristem into a reproductive fate in the determinate genotype GNIB 21. The splice site SNP leads to absence of 14 amino acids in mutant TFL protein of GNIB 21, rendering the protein non-functional. This deletion disturbed previously reported anion-binding pocket and secondary binding pocket due to displacement of small ß-sheet away from an external loop. This finding may enable the modulation of growth habit in Indian bean and other pulse crops through genome editing.

Associating gene expressions with curcuminoid biosynthesis in turmeric.

BACKGROUND: Biologically important curcuminoids viz curcumin, demethoxycurcumin, and bisdemethoxycurcumin in turmeric rhizome have several health benefits. Pharmaceutical industries synthesize curcuminoids manipulating gene expressions in vitro or in vivo because of their medicinal importance. In this experiment, we studied the gene expressions involved in the curcuminoid biosynthesis pathway in association with curcuminoid yield in turmeric rhizome to study the impact of individual gene expression on curcuminoid biosynthesis. RESULTS: Gene expressions at the different growth stages of turmeric rhizome were association tested with respective curcuminoid contents. Gene expression patterns of diketide-CoA synthase (DCS) and multiple curcumin synthases (CURSs) viz curcumin synthase 1 (CURS1), curcumin synthase 2 (CURS2), and curcumin synthase 3 (CURS3) were differentially associated with different curcuminoid contents. Genotype and growth stages showed a significant effect on the gene expressions resulting in a significant impact on curcuminoid balance in turmeric rhizome. DCS and CURS3 expression patterns were similar but distinct from CURS1 and CURS2 expression patterns in turmeric rhizome. DCS expression had a significant positive and CURS3 expression had a significant negative association with curcumin, demethoxycurcumin, bisdemethoxycurcumin, and total curcuminoid in turmeric rhizome. CURS1 expression had a negative association with curcumin whereas CURS2 expression showed a positive association with demethoxycurcumin. CONCLUSIONS: The effects of DCS and CURS expressions are not always positive with different curcuminoid contents in turmeric rhizome. DCS expression has a positive and CURS3 expression has a negative association with curcuminoids. CURS1 and CURS2 are also associated with curcumin and demethoxycurcumin synthesis. This mechanism of co-expression of diketide-CoA synthase and multiple curcumin synthases in turmeric rhizome has a significant effect on curcuminoid balance in different turmeric cultivars. Further experiment will explore more insights; however, association-based test results from this experiment can be useful in improving curcuminoid yield in turmeric rhizome or in vitro through the application of genetic engineering and biotechnology. Associating gene expressions with curcuminoid biosynthesis in turmeric.

Multisystem Imaging Manifestations of COVID-19, Part 2: From Cardiac Complications to Pediatric Manifestations.

Infection with severe acute respiratory syndrome coronavirus 2 results in coronavirus disease 2019 (COVID-19), which was declared an official pandemic by the World Health Organization on March 11, 2020. COVID-19 has been reported in most countries, and as of August 15, 2020, there have been over 21 million cases of COVID-19 reported worldwide, with over 800 000 COVID-19-associated deaths. Although COVID-19 predominantly affects the respiratory system, it has become apparent that many other organ systems can also be involved. Imaging plays an essential role in the diagnosis of all manifestations of the disease and its related complications, and proper utilization and interpretation of imaging examinations is crucial. A comprehensive understanding of the diagnostic imaging hallmarks, imaging features, multisystem involvement, and evolution of imaging findings is essential for effective patient management and treatment. In part 1 of this article, the authors described the viral pathogenesis, diagnostic imaging hallmarks, and manifestations of the pulmonary and peripheral and central vascular systems of COVID-19. In part 2 of this article, the authors focus on the key imaging features of the varied pathologic manifestations of COVID-19, involving the cardiac, neurologic, abdominal, dermatologic and ocular, and musculoskeletal systems, as well as the pediatric and pregnancy-related manifestations of the virus. Online supplemental material is available for this article. ©RSNA, 2020.

Multisystem Imaging Manifestations of COVID-19, Part 1: Viral Pathogenesis and Pulmonary and Vascular System Complications.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in coronavirus disease 2019 (COVID-19), which was declared an official pandemic by the World Health Organization on March 11, 2020. The infection has been reported in most countries around the world. As of August 2020, there have been over 21 million cases of COVID-19 reported worldwide, with over 800 000 COVID-19-associated deaths. It has become apparent that although COVID-19 predominantly affects the respiratory system, many other organ systems can also be involved. Imaging plays an essential role in the diagnosis of all manifestations of the disease, as well as its related complications, and proper utilization and interpretation of imaging examinations is crucial. With the growing global COVID-19 outbreak, a comprehensive understanding of the diagnostic imaging hallmarks, imaging features, multisystemic involvement, and evolution of imaging findings is essential for effective patient management and treatment. To date, only a few articles have been published that comprehensively describe the multisystemic imaging manifestations of COVID-19. The authors provide an inclusive system-by-system image-based review of this life-threatening and rapidly spreading infection. In part 1 of this article, the authors discuss general aspects of the disease, with an emphasis on virology, the pathophysiology of the virus, and clinical presentation of the disease. The key imaging features of the varied pathologic manifestations of this infection that involve the pulmonary and peripheral and central vascular systems are also described. Part 2 will focus on key imaging features of COVID-19 that involve the cardiac, neurologic, abdominal, dermatologic and ocular, and musculoskeletal systems, as well as pediatric and pregnancy-related manifestations of the virus. Vascular complications pertinent to each system will be also be discussed in part 2. Online supplemental material is available for this article. ©RSNA, 2020.

Clinical Characteristics and Long-Term Outcomes of Midaortic Syndrome.

BACKGROUND: Midaortic syndrome (MAS) is a rare congenital or acquired condition marked by segmental or diffuse stenosis of the distal thoracic and/or abdominal aorta and its branches. The optimal approach to medical or interventional management of MAS and long-term outcomes in adults are not well defined. We reviewed MAS cases to characterize the natural history of aortic disease, identify prognostic factors, and evaluate the durability of invasive interventions. METHODS: We conducted a retrospective review of patients with MAS who presented to Memorial Hermann Hospital and Baylor College of Medicine between 1997 and 2018. We categorized cases according to demographic and clinical manifestations, etiologies, the extent of aortic involvement, interventions, and vascular outcomes. RESULTS: We identified a cohort of 13 patients with MAS. The etiology of MAS was identified in 6 cases, including genetic syndromes (neurofibromatosis type 1 (2/13), Williams syndrome (1/13), fibromuscular dysplasia (2/13), and Takayasu arteritis (1/13)). Mean age at first documented clinical event was 25.2 (2-67) years, but cases with genetic etiologies presented significantly younger (18.2 years). The most common primary anatomic site was the suprarenal and infrarenal aorta (zones 5-8). Extra-aortic locations involved the renal (4/13), celiac (3/13), and superior mesenteric (3/13) arteries. Clinical manifestations included hypertension (13/13), claudication (9/13), and postprandial abdominal pain (5/13). All patients with available follow-up data underwent at least one surgical or endovascular intervention (range: 1-8). Postoperative complications included renal failure requiring postdischarge hemodialysis and respiratory failure. There were no deaths in long-term follow-up. CONCLUSIONS: MAS is a complex vasculopathy with substantial variability in clinical presentation and anatomic distribution. Extensive disease frequently requires multiple invasive interventions and results in refractory hypertension, which may predict subsequent clinical events. A multidisciplinary approach with long-term monitoring is essential for preservation of end-organ function and quality of life in this debilitating disease.

Diffuse melanosis cutis: a rare manifestation of metastatic melanoma.

Diffuse melanosis cutis (DMC) is an extremely rare and late complication of metastatic melanoma (MM). It involves the progressive blue-grey discolouration of the skin and mucous membranes, occurring approximately 1 year after diagnosis of MM. The pathogenesis of DMC is unknown, although specific growth factors, such as alpha-melanocyte stimulating hormone, hepatocyte growth factor and endothelin-1, released by cancer cells, along with release of melanin precursors in the bloodstream and dermal MM micrometastases producing melanin have been attributed. Even with appropriate therapy, DMC seems to be a poor prognostic factor, with a mean survival time of 4-5 months. Here, we report a case of BRAF-mutated MM who presented with DMC. The patient underwent BRAF/MEK inhibition followed by anti-PDL1 therapy, yet passed away approximately 1 year after diagnosis.