Low-dose, high-pitch, spiral (FLASH) mode versus conventional sequential method for coronary artery calcium scoring: A derivation-validation study.

Introduction: The present study sought to compare the diagnostic accuracy and radiation dose of ECG-gated, ultra-fast, low-dose, high-pitch, spiral (FLASH) mode versus conventional, ECG-gated, sequential coronary artery calcium (CAC) scoring in patients with suspected coronary artery disease (CAD). Methods: The study included 120 patients who underwent both conventional scanning and FLASH mode scanning and were subdivided into derivation and validation cohorts. In the conventional sequential (step-and-shoot) protocol, prospective ECG-gated, non-contrast acquisition was performed at 70% of R-R interval. The spiral (FLASH) mode utilized a high-pitch and high-speed gantry rotation scanning mode where acquisition of the entire heart was done within a single cardiac cycle with prospective ECG-gating at 70% of R-R interval. Results: Correlation between CAC scores derived from conventional (cCAC) and FLASH mode (fCAC) in derivation cohort was excellent (r=0.99; P<0.001). A linear regression model was used to develop a formula for deriving the estimated CAC score (eCAC) from fCAC (eCAC=0.978 x fCAC). In validation cohort, eCAC showed excellent agreement with cCAC (ICC=0.9983; 95%CI: 0.9972 - 0.9990). Excellent agreement for risk classification (weighted kappa=0.93898; 95%CI: 0.86833 - 1.0000) was observed with 95% (57/60) scores falling within the same risk category. Effective dose was significantly lower in FLASH mode (conventional, 0.58±0.21 mSv vs. FLASH, 0.34±0.12 mSv; P<0.0001). Conclusion: CAC scoring using FLASH mode is feasible with high accuracy and shows excellent agreement with conventional CAC scores at significantly reduced radiation doses.

Feasibility of a "No-Biopsy" Approach for the Diagnosis of Celiac Disease in Symptomatic Adults.

Celiac disease (CD) is an immune-mediated enteropathy, caused by hypersensitivity to gluten in genetically predisposed individuals. The worldwide prevalence of CD has been estimated to be approximately 1%. Most guidelines for diagnosis of CD rely on a sequential approach, with serological testing of antibodies against tissue transglutaminase (tTG) as a first-line test, followed by a duodenal biopsy. However, GI biopsy is an invasive procedure with various complications. Hence, this study was planned to ascertain whether it could be possible to have a non-biopsy approach, using only serological markers to establish the diagnosis of CD in adults. MATERIAL AND METHODS: It was a retrospective analysis of medical records of all biopsy-diagnosed CD patients with available anti-tTGA antibodies reports from 2019 to 2023. The patients were divided into three groups based on Marsh grading and anti-tTGA antibody levels were compared using various statistical tests. RESULTS: A total of 94 biopsy-diagnosed symptomatic CD patients with anti-tTGA antibody reports available formed the study group. Of these, 54 had biopsy findings consistent with Marsh 3 lesion, three had Marsh 2 lesion, and 37 had Marsh 1 lesion. A significant correlation existed between Marsh grading 3 lesion and anti-tTGA antibody levels above the upper limit of normal (ULN) x 10. CONCLUSION: Serum levels of anti-tTGA antibodies greater than 10 x ULN can be used to identify symptomatic patients with Marsh grade 3 CD lesions.

Amycolatopsis mediterranei: A Sixty-Year Journey from Strain Isolation to Unlocking Its Potential of Rifamycin Analogue Production by Combinatorial Biosynthesis.

Ever since the isolation of Amycolatopsis mediterranei in 1957, this strain has been the focus of research worldwide. In the last 60 years or more, our understanding of the taxonomy, development of cloning vectors and conjugation system, physiology, genetics, genomics, and biosynthetic pathway of rifamycin B production in A. mediterranei has substantially increased. In particular, the development of cloning vectors, transformation system, characterization of the rifamycin biosynthetic gene cluster, and the regulation of rifamycin B production by the pioneering work of Heinz Floss have made the rifamycin polyketide biosynthetic gene cluster (PKS) an attractive target for extensive genetic manipulations to produce rifamycin B analogues which could be effective against multi-drug-resistant tuberculosis. Additionally, a better understanding of the regulation of rifamycin B production and the application of newer genomics tools, including CRISPR-assisted genome editing systems, might prove useful to overcome the limitations associated with low production of rifamycin analogues.

Longitudinal Associations of Diet, Food Insecurity, and Supplemental Nutrition Assistance Program Use with Global Cognitive Performance in Middle-Aged and Older Adults.

BACKGROUND: Diet quality, food access, and food assistance policies may be key modifiable factors related to cognitive decline. OBJECTIVE: We aimed to evaluate whether diet quality, food insecurity, and Supplemental Nutrition Assistance Program (SNAP) use are associated with longitudinal changes in cognition among older adults in the United States. METHODS: Food intake data from the Health Care and Nutrition Study were linked with longitudinal health information from 5 waves of the Health and Retirement Study (2012-2020). The analytic sample (n = 6968) included community-dwelling United States adults aged ≥51 y without cognitive impairment. Global cognition was measured using a telephone-based cognitive status interview (range: 0-27). Diet quality was measured with the Healthy Eating Index, using participants' average intake of 13 dietary components. Questions regarding food access and affordability were used to determine food insecurity and use of SNAP benefits. Linear mixed-effects regression models were used to estimate longitudinal associations between diet-related factors and cognitive score changes. RESULTS: Poorer diets [ß: -0.24; 95% confidence interval (CI): -0.33, -0.15], food insecurity (ß: -1.08; 95% CI: -1.31, -0.85), and SNAP use (ß: -0.57; 95% CI: -0.82, -0.32) were associated with lower baseline cognitive scores. Poorer diets (ß: -0.17; 95% CI: -0.29, -0.05) and food insecurity (ß: -0.23; 95% CI: -0.47, -0.01) were associated with significantly steeper declines in cognitive scores over time, after 8 and 2 y of follow-up, respectively; however, SNAP use was not significantly associated with the rate of cognitive decline over time. Estimates were qualitatively similar when restricting the sample to participants aged ≥65 y. CONCLUSIONS: Results suggest that food access and adherence to healthy diet recommendations may be important elements to maintain cognitive health in aging. SNAP benefits may be insufficient to prevent negative cognitive effects of poor diet and limited access to nutritious foods.

Genome-wide regulation of Pol II, FACT, and Spt6 occupancies by RSC in Saccharomyces cerevisiae.

RSC (remodels the structure of chromatin) is an essential ATP-dependent chromatin remodeling complex in Saccharomyces cerevisiae. RSC utilizes its ATPase subunit, Sth1, to slide or remove nucleosomes. RSC has been shown to regulate the width of the nucleosome-depleted regions (NDRs) by sliding the flanking nucleosomes away from NDRs. As such, when RSC is depleted, nucleosomes encroach NDRs, leading to transcription initiation defects. In this study, we examined the effects of the catalytic-dead Sth1 on transcription and compared them to those observed during acute and rapid Sth1 depletion by auxin-induced degron strategy. We found that rapid depletion of Sth1 reduces recruitment of TBP and Pol II in highly transcribed genes, as would be expected considering its role in regulating chromatin structure at promoters. In contrast, cells harboring the catalytic-dead Sth1 (sth1-K501R) exhibited a severe reduction in TBP binding, but, surprisingly, also displayed a substantial accumulation in Pol II occupancies within coding regions. The Pol II occupancies further increased upon depleting endogenous Sth1 in the catalytic-dead mutant, suggesting that the inactive Sth1 contributes to Pol II accumulation in coding regions. Notwithstanding the Pol II increase, the ORF occupancies of histone chaperones, FACT and Spt6 were significantly reduced in the mutant. These results suggest a potential role for RSC in recruiting/retaining these chaperones in coding regions. Pol II accumulation despite substantial reductions in TBP, FACT, and Spt6 occupancies in the catalytic-dead mutant could indicate severe transcription elongation and termination defects. Such defects would be consistent with studies showing that RSC is recruited to coding regions in a transcription-dependent manner. Thus, these findings imply a role for RSC in transcription elongation and termination processes, in addition to its established role in transcription initiation.

A Domain-Shift Invariant CNN Framework for Cardiac MRI Segmentation Across Unseen Domains.

The emergence of various deep learning approaches in diagnostic medical image segmentation has made machines capable of accomplishing human-level accuracy. However, the generalizability of these architectures across patients from different countries, Magnetic Resonance Imaging (MRI) scans from distinct vendors, and varying imaging conditions remains questionable. In this work, we propose a translatable deep learning framework for diagnostic segmentation of cine MRI scans. This study aims to render the available SOTA (state-of-the-art) architectures domain-shift invariant by utilizing the heterogeneity of multi-sequence cardiac MRI. To develop and test our approach, we curated a diverse group of public datasets and a dataset obtained from private source. We evaluated 3 SOTA CNN (Convolution neural network) architectures i.e., U-Net, Attention-U-Net, and Attention-Res-U-Net. These architectures were first trained on a combination of three different cardiac MRI sequences. Next, we examined the M&M (multi-center & mutli-vendor) challenge dataset to investigate the effect of different training sets on translatability. The U-Net architecture, trained on the multi-sequence dataset, proved to be the most generalizable across multiple datasets during validation on unseen domains. This model attained mean dice scores of 0.81, 0.85, and 0.83 for myocardial wall segmentation after testing on unseen MyoPS (Myocardial Pathology Segmentation) 2020 dataset, AIIMS (All India Institute of Medical Sciences) dataset and M&M dataset, respectively. Our framework achieved Pearson's correlation values of 0.98, 0.99, and 0.95 between the observed and predicted parameters of end diastole volume, end systole volume, and ejection fraction, respectively, on the unseen Indian population dataset.

A large cardiac tuberculoma masquerading a malignant mass in a 15-year-old boy.

We hereby present a case of large cardiac tuberculoma which was thought to be a malignant mass on cardiac magnetic resonance imaging (MRI). The present case highlights that high index of suspicion is necessary to diagnose this rare entity especially in tuberculosis-endemic areas, or in those who have relevant past history of this condition.

Lung water estimation on cardiac magnetic resonance imaging for predicting adverse cardiovascular outcomes in patients with heart failure.

OBJECTIVES: Pulmonary congestion is a central feature of heart failure (HF) seen in acute decompensated state as well as in chronic stable disease. The present study sought to determine whether simplified cardiac magnetic resonance imaging (CMR)-derived lung water density (LWD) measurement has prognostic relevance in predicting adverse cardiovascular outcomes in patients with HF and left ventricular ejection fraction (LVEF)<50%. METHODS: Eighty consecutive patients referred for CMR with HF and LVEF<50% along with 22 healthy age- and sex-matched controls were prospectively recruited. LWD was the lung-to-liver signal intensity ratio multiplied by 70% (estimated hepatic water density). The primary endpoint was composite of all-cause mortality or HF-related hospitalization within 6 months from CMR. RESULTS: The mean LWD was significantly higher in HF patients compared to healthy controls (19.78 ± 6.1 vs 13.6 ± 2.3; p < 0.001). The mean LWD was significantly different among patients with NYHA class I/II and NYHA class III/IV (17.88 ± 4.8 vs 21.77 ± 1.08; p = 0.004). At 6 months, the primary endpoint was reached in 12 (15%) patients. Patients with "wet lungs" (LWD > 18.1%) had higher incidence of adverse cardiovascular outcomes compared to patients with "dry lungs". LWD was an independent predictor of adverse cardiovascular outcomes in multivariable analysis. At the optimal cut-off of LWD > 23.38%, the sensitivity and specificity were 91.67 and 91.18%, respectively, to predict adverse cardiovascular outcomes. CONCLUSION: LWD on CMR is independently associated with increased risk of mortality and HF-related hospitalization in HF patients with LVEF<50%. ADVANCES IN KNOWLEDGE: Non-invasive quantitative estimation of LWD on CMR can improve risk stratification and guide management in HF patients.

Comparative docking studies of drugs and phytocompounds for emerging variants of SARS-CoV-2.

In the last three years, COVID-19 has impacted the world with back-to-back waves leading to devastating consequences. SARS-CoV-2, the causative agent of COVID-19, was first detected in 2019 and since then has spread to 228 countries. Even though the primary focus of research groups was diverted to fight against COVID-19, yet no dedicated drug has been developed to combat the emergent life-threatening medical conditions. In this study, 35 phytocompounds and 43 drugs were investigated for comparative docking analysis. Molecular docking and virtual screening were performed against SARS-CoV-2 spike glycoprotein of 13 variants using AutoDock Vina tool 1.5.6 and Discovery Studio, respectively, to identify the most efficient drugs. Selection of the most suitable compounds with the best binding affinity was done after screening for toxicity, ADME (absorption, distribution, metabolism and excretion) properties and drug-likeliness. The potential candidates were discovered to be Liquiritin (binding affinities ranging between -7.0 and -8.1 kcal/mol for the 13 variants) and Apigenin (binding affinities ranging between -6.8 and -7.3 kcal/mol for the 13 variants) based on their toxicity and consistent binding affinity with the Spike protein of all variants. The stability of the protein-ligand complex was determined using Molecular dynamics (MD) simulation of Apigenin with the Delta plus variant of SARS-CoV-2. Furthermore, Liquiritin and Apigenin were also found to be less toxic than the presently used drugs and showed promising results based on in silico studies, though, confirmation using in vitro studies is required. This in-depth comparative investigation suggests potential drug candidates to fight against SARS-CoV-2 variants. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03450-6.

Evaluation of aortopulmonary window using virtual dissection of multidetector computed tomography angiography data sets.

AIM: The present study sought to evaluate the morphology and associated cardiovascular anomalies in patients with aortopulmonary window on virtual dissection of multidetector computed tomography (CT) angiography data sets. MATERIAL AND METHODS: We conducted a retrospective search of our departmental database from January 2014 to September 2021 to identify patients with aortopulmonary window and relevant information was extracted from the electronic case records and from routine examination as well as virtual dissection of CT data sets. RESULTS: An aortopulmonary window was observed in 26 patients (20 males; 6 females). Based on location of the defect, a distal aortopulmonary window was the most common subtype, seen in 13/26 (50%) patients followed by a proximal, complete and intermediate subtypes seen in 7/26 (27%), 5/26 (19%) and 1/26 (4%) patients respectively. Associated ventricular septal defect was observed in 9/26 (34.6%) patients while an interrupted aortic arch was present in 5/26 (19.2%) patients. Tetralogy of Fallot was seen in 5/26 (19.2%) patients. Anomalous origin of right pulmonary artery from ascending aorta and crossed pulmonary arteries were seen in 2/26 (7.6%) patients each. An isolated aortopulmonary window without any simple/complex congenital anomaly was seen in 10/26 (38.5%) patients. CONCLUSION: Aortopulmonary window is associated with a wide gamut of cardiovascular lesions, with ventricular septal defect being the commonest associated anomaly followed by tetralogy of Fallot and interrupted aortic arch respectively. Virtual dissection of multidetector CT angiography allows detailed anatomical evaluation of aortopulmonary window, allowing a clear visualization of the defect and associated cardiovascular anomalies.

External iliac artery Endofibrosis in a professional cyclist.

We present a case of a 30-year-old female professional cyclist who presented with right thigh claudication while performing high-intensity efforts. Based on the typical clinical history and the presence of a smooth long segment diffuse narrowing in the right external iliac artery on non-contrast magnetic resonance angiography, a diagnosis of external iliac artery endofibrosis or "cyclist's iliac syndrome" was made. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-022-01349-8.

MoCA in five Indian languages: A brief screening tool to diagnose dementia and MCI in a linguistically diverse setting.

INTRODUCTION AND OBJECTIVES: Early dementia diagnosis in low and middle-income countries (LMIC) is challenging due to limited availability of brief, culturally appropriate, and psychometrically validated tests. Montreal Cognitive Assessment (MoCA) is one of the most widely used cognitive screening tests in primary and secondary care globally. In the current study, we adapted and validated MoCA in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam) and determined the optimal cut-off points that correspond to screening for clinical diagnosis of dementia and MCI. METHODS: A systematic process of adaptation and modifications of MoCA was fulfilled. A total of 446 participants: 214 controls, 102 dementia, and 130 MCI were recruited across six centers. RESULTS: Across five languages, the area under the curve for diagnosis of dementia varied from 0.89 to 0.98 and MCI varied from 0.73 to 0.96. The sensitivity, specificity and optimum cut-off scores were established separately for five Indian languages. CONCLUSIONS: The Indian adapted MoCA is standardized and validated in five Indian languages for early diagnosis of dementia and MCI in a linguistically and culturally diverse population.

Efficacy and Safety of Venous Sac Embolization With or Without Feeding Artery Embolization Versus Feeding Artery Embolization Alone in the Management of Pulmonary Arteriovenous Malformations: A Systematic Review and Meta-analysis.

PURPOSE: To evaluate by meta-analysis the safety and efficacy of venous sac embolization (VSE) with or without feeding artery embolization versus feeding artery embolization (FAE) alone in the management of pulmonary arteriovenous malformations (PAVMs). METHODS: This systematic review and meta-analysis was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic literature search was performed in MEDLINE, Embase, and Scopus till August 31, 2021 to identify studies comparing the safety and efficacy of VSE with or without FAE versus FAE alone in PAVMs. The success of treatment was assessed by comparing the number of PAVMs with ≥70% decrease in the size of draining vein/sac between the 2 groups. The pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using the random-effects inverse-variance model and were used to compare pooled therapeutic efficacy between the groups. RESULTS: Three studies were found eligible for the meta-analysis. The included studies had a total of 169 patients (119 females and 50 males). The total number of PAVMs was 298, and hereditary hemorrhagic telangiectasia was present in 119 patients. The success of treatment was higher with VSE as compared to FAE (OR=3.54, 95% CI=1.66-7.56). The minor complications were similar in both groups, and one major complication occurred in the FAE group. More coils were used in the VSE group. CONCLUSIONS: The present systematic review and meta-analysis has consolidated the evidence that VSE with or without FAE is more efficacious than FAE alone in the management of PAVMs without any increase in the associated risk of sac rupture or coil migration. CLINICAL IMPACT: Until high-quality data from a prospective, multicentric, randomized controlled trial becomes available, the evidence consolidated by the present systematic review and meta-analysis showing the efficacy of venous sac embolization (with or without feeding artery embolization) over feeding artery embolization alone, can be used for clinical decision-making in the management of pulmonary arterio-venous malformations.

Developmental Anomalies of the Inferior Vena Cava and its Tributaries: What the Radiologist Needs to Know?

Inferior vena cava (IVC) can be involved by a wide gamut of developmental anomalies owing to its complex embryogenesis. Developmental anomalies of the IVC are not infrequent, seen in approximately 8.7% of the general population. Although most of the anatomical variations are asymptomatic, identification of these variations is important before planning any vascular surgery or interventional procedure in relation to the IVC to avoid inadvertent complications. Conventional venography has largely been replaced by noninvasive cross-sectional imaging modalities for detecting IVC abnormalities. Ultrasonography, often used for initial evaluation, is highly operator-dependent and the infrarenal part of IVC is often obscured by bowel gases. While magnetic resonance imaging is devoid of radiation risks, its use is limited due to limited availability and the frequent need for sedation. Computed tomography (CT) venography plays a pivotal role in the detection of these anomalies as it has an excellent spatial resolution along with availability of multiple postprocessing tools such as multiplanar reconstruction with generation of maximum intensity projection and volume-rendered images. This pictorial review focuses on the embryogenesis of IVC, various developmental anomalies of the IVC and its tributaries, their appearance on CT venography and conceivable clinical relevance.

Microbial Journey: Mount Everest to Mars.

A rigorous exploration of microbial diversity has revealed its presence on Earth, deep oceans, and vast space. The presence of microbial life in diverse environmental conditions, ranging from moderate to extreme temperature, pH, salinity, oxygen, radiations, and altitudes, has provided the necessary impetus to search for them by extending the limits of their habitats. Microbiology started as a distinct science in the mid-nineteenth century and has provided inputs for the betterment of mankind during the last 150 years. As beneficial microbes are assets and pathogens are detrimental, studying both have its own merits. Scientists are nowadays working on illustrating the microbial dynamics in Earth's subsurface, deep sea, and polar regions. In addition to studying the role of microbes in the environment, the microbe-host interactions in humans, animals and plants are also unearthing newer insights that can help us to improve the health of the host by modulating the microbiota. Microbes have the potential to remediate persistent organic pollutants. Antimicrobial resistance which is a serious concern can also be tackled only after monitoring the spread of resistant microbes using disciplines of genomics and metagenomics The cognizance of microbiology has reached the top of the world. Space Missions are now looking for signs of life on the planets (specifically Mars), the Moon and beyond them. Among the most potent pieces of evidence to support the existence of life is to look for microbial, plant, and animal fossils. There is also an urgent need to deliberate and communicate these findings to layman and policymakers that would help them to take an adequate decision for better health and the environment around us. Here, we present a glimpse of recent advancements by scientists from around the world, exploring and exploiting microbial diversity.

A rare pediatric case of pedunculated cardiac hemangioma of the left ventricle.

A 12-year-old male child with atypical chest pain and fatigue since past 3 months underwent cardiac magnetic resonance (CMR) imaging for suspicious globular mobile mass detected in the left ventricle on a transthoracic echocardiography. CMR revealed peripheral vascular blush on the first pass perfusion images with centripetal progressive intensely bright enhancement on late gadolinium-enhanced images. Further confirmation and histological diagnosis of the tumor was made through transaortic aortic resection of the mass.

Association between aortic coverage and spinal cord ischemia after endovascular repair of type B aortic dissection.

Objectives: To examine the association between aortic coverage and occurrence of spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection. Methods: Thirty-eight consecutive patients (mean age 52 years; 35 men) who underwent TEVAR for type B aortic dissection at our centre were included. Patients were stratified into two groups based on stent graft length (SGL): group I (≤ 200 mm; n = 19) and group II (> 200 mm; n = 19). All the procedures were performed under strict blood pressure monitoring. Preoperative cerebrospinal fluid (CSF) drain was instituted in two patients. Results: Mean SGLs were 200 mm in group I and 277 ± 27 mm in group II. The number of segmental arteries covered was significantly different between the two groups (p < 0.001). There was no significant difference in vertebral artery dominance between groups I and II (p = 0.99). One patient in group II, who also had bilateral internal iliac artery occlusion, developed postprocedural neurological deficit referrable to SCI, which resolved completely after institution of CSF drainage. However, the incidence of SCI was not significantly different between group I and group II (p = 0.5). Conclusion: Based on our experience, we recommend longer aortic coverage (beyond 200 mm) in type B aortic dissection (TBAD) for better aortic remodelling, provided that the mean arterial pressure of > 90 mm Hg is maintained perioperatively to avoid SCI.

Phylogenomics of the Phylum Proteobacteria: Resolving the Complex Relationships.

Proteobacteria is one of the largest and phenotypically most diverse divisions within the domain bacteria. Due to the economic importance, this phylum demands an urgent need for a clear and scientifically sound classification system to streamline their characterization. The goal of our study was to carefully reevaluate the current system of classification and suggest changes wherein necessary. Phylogenetic trees of 84 Proteobacteria were constructed using single gene-based phylogeny involving 16S rRNA genes and protein sequences of 85 conserved genes, whole genome-based phylogenetic tree using CVtree3.0, amino acid Identity matrix tree, and concatenated tree with aforementioned conserved genes. The results of our study confirm the polyphyletic relationship between Desulfurella acetivorans, a Deltaproteobacteria with Epsilonproteobacteria. The group Syntrophobacterales was found to be polyphyletic with respect to Desulfarculus baarsii and the group Thiotrichales was found to be splitting in different phylogenetic trees. Placement of phylogenetic groups belonging to Rhodocyclales, Oceonospirilalles, and Chromatiales is controversial and requires further study and revisions. Based on our analysis, we strongly support reclassification of Magnetococcales as a separate class Etaproteobacteria. From our results, we conclude that concatenated trees of conserved proteins are a more accurate method for phylogenetic analysis, as compared to other methods used.

Left pulmonary veins draining into persistent left superior caval vein in presence of unroofed coronary sinus.

We report a case of 5-year-old girl with double outlet right ventricle with a rare combination of partial anomalous pulmonary venous drainage into a persistent left superior caval vein in the presence of an unroofed coronary sinus while highlighting its possible embryological origins and therapeutic implications.