Background: Transesophageal echocardiogram (TEE) is the gold-standard for diagnosis of degenerative mitral regurgitation (MR) and is used for guidance of transcatheter mitral valve repair (TMVr). However, TEE is an invasive diagnostic modality that requires anesthesia and esophageal intubation. Multi-detector computed tomographic angiography (MDCT) provides high resolution images and three dimensional (3D) reconstructions that allow for comprehensive assessment of complex mitral anatomy. We hypothesized that MDCT can yield similar information to 3D TEE relevant to TMVr, deferring the need for a preoperative TEE. Methods: Patients that underwent TMVr (or were evaluated for transcatheter mitral valve replacement) for degenerative MR were retrospectively analyzed from 2017 to 2019 at a single center. Patients were included in the analysis if preoperative MDCT was performed. Two experienced TEE and two MDCT readers, blinded to patient outcome and alternative imaging modality, analyzed the following characteristics: leaflet pathology (flail, degenerative, mixed), leaflet location (A1-3/P1-3), mitral valve area (MVA), flail width/gap, anterior-posterior (AP) and commissural diameters, posterior leaflet length, leaflet thickness, presence of mitral valve cleft and degree of mitral annular calcification (MAC). Results: Of the 87 patients, 22 had preoperative MDCT. MDCT was able to correctly identify the leaflet pathology in 77% (17/22). Eleven patients had a flail leaflet with 91% (10/11) identified on MDCT and MDCT correctly predicted the dysfunctional leaflet location in 95% (21/22). Measurements were not significantly different for MVA, flail width, commissural diameter, AP diameter, posterior leaflet length and leaflet thickness. However, measurements on MDCT were significantly overestimated for flail gap compared to TEE. Degree of MAC was similar in 91% (10/11) between imaging modalities. Conclusion: MDCT provides similar measurements to 3D TEE for preoperative TMVr planning. Further studies are required to establish novel imaging algorithms utilizing MDCT to reduce the need for preoperative TEE.

Pathogenic variants in JAG1 are known to cause Alagille syndrome (ALGS), a disorder that primarily affects the liver, lung, kidney and skeleton. Whereas cardiac symptoms are also frequently observed in ALGS, thoracic aortic aneurysms have only been reported sporadically in post-mortem autopsies. We here report two families with segregating JAG1 variants that present with isolated aneurysmal disease, as well as the first histological evaluation of aortic aneurysm tissue of a JAG1 variant carrier. Our observations shed more light on the pathomechanisms behind aneurysm formation in JAG1 variant carriers and underline the importance of cardiovascular imaging in the clinical follow-up of JAG1 variant carrying individuals.

An 82-year old woman with third degree atrioventricular block underwent left bundle branch area pacing (LBBAP) lead implantation

Background: The risk factors for mucus plug in children with adenovirus (ADV) pneumonia. Methods and materials：A retrospective analysis was conducted of children diagnosed ADV pneumonia and underwent bronchoscopy. The patients were divided into a mucus plug group (39 cases) and a non-mucus plug group (53 cases). The children’s data including sex, age, clinical presentation, laboratory test parameters, imaging and bronchoscopic data were collected. The risk factors for the development of airway mucus plug were analysed by multifactorial logistic regression. Results: There were no statistically significant differences in sex, age, fever, hospitalization days, mixed infection, WBC count, neutrophil proportion, CRP, and D-dimer (all P>0.05); Thermal range, calcineurin (PCT), lactate dehydrogenase (LDH), Pleural effusion and associated decreased breath sounds was significantly higher in mucus plug group than in non-mucus plug group; multifactorial logistic regression analysis showed that the duration of fever, PCT, and LDH were independent risk factors for the formation of mucus plugs. The critical values of ROC curves were pyroprocedure ≥6.5 d, PCT ≥0.705 ng/ml and LDH ≥478.5 U/L. Conclusion: Duration of fever, PCT and LDH levels were the independent risk factors for the formation of an airway mucus plug in children with ADV pneumonia.

Pain in children living with and beyond cancer is understudied and undertreated. Pain science education (PSE) is a conceptual change strategy facilitating patients’ understanding of the biopsychosocial aspects of pain. Preliminary studies on the adaptation of PSE interventions to adults with and beyond cancer provide a foundation for pediatric research. PSE could help childhood cancer survivors experiencing persistent pain and pain-related worry after active treatment. PSE may also help children receiving cancer treatment, providing them with a foundation of adaptive pain beliefs and cognitions, and preparing them for procedural and treatment-related pain. We direct this paper towards pediatric oncology clinicians, policy makers and researchers working with children living with and beyond cancer. We aim to; (1) identify challenges in adapting PSE for children living with and beyond cancer, (2) offer possible solutions, and (3) propose research questions to guide the implementation of PSE for children living with and beyond cancer.

Objectives: To examine the association between racial origin and preeclampsia(PE) and gestational hypertension(GH) after adjustment for factors in maternal characteristics and medical history in screening study from the Fetal Medicine Foundation (FMF) in England, and to perform a systematic review and meta-analysis of studies on PE. Methods: In the FMF data regression analysis was performed to examine the association between racial origin and PE or GH. Literature search to December 2021 was carried out to identify peer-reviewed publications on race and PE. Main outcome measure: Relative risk of PE and GH in women of black, South Asian and East Asian racial origin by comparison to white women. Results: In the FMF study there were 168,966 singleton pregnancies without major abnormalities delivering at ≥24 weeks’ gestation. In black women the respective risk of total-PE and preterm-PE was 2-fold and 2.5-fold higher and risk of GH was 25% higher, in South Asian women there was a 1.5-fold higher risk of preterm-PE but not total-PE, and in East Asian women there was no significant difference in risk of hypertensive disorders. The literature search identified 19 studies that provided data on several million of pregnancies, but 17 were at moderate or high-risk of bias and only three provided risks adjusted for some maternal characteristics; consequently, these studies did not provide accurate contribution of different racial groups to the prediction of PE. Conclusion: In women of black and South Asian origin the risk of PE, after adjustment for confounders, is higher than in white women

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Title: The Fa(r)st or the Spurious - Pulmonary vein cycle length – Is it the fuel driving persistent AF, or simply just fumes?Authors: Sandeep Prabhu1,2,3 and Louise Segan1,2,3

Abstracts from the 27th Annual International Atrial Fibrillation Symposium January 13-15, 2022

Background and Purpose: Piezo1 is a crucial mechanical sensitive channel involved in vascular remodeling. However, the role of Piezo1 in different types of vascular cells during the development of pulmonary hypertension (PH) induced by high flow is largely unknown. Experimental Approach: Based on previously established protocols, we established a rat PH model by left pulmonary artery ligation (LPAL) for 2 and 5 weeks to mimic the high flow and hemodynamic stress. Key Results: Results showed that right ventricular systolic pressure (RVSP) and right ventricular wall thickness were significantly increased in the LPAL groups compared with the SHAM group. Rats in LPAL-5w groups developed remarkable pulmonary vascular remodeling, resulting in decreased phenylephrine-induced contraction and acetylcholine-induced relaxation. On the one hand, in pulmonary arterial smooth muscle cells (PASMCs), upregulation of Piezo1 was observed in association with the elevation of [Ca2+]cyt in the PASMCs from both LPAL-2w and LPAL-5w groups versus respective SHAM groups. Notably, Piezo1 expression was directly upregulated by YAP/TEAD4. On the other hand, significantly upregulated Piezo1 expression was also presented in the lung tissues, mostly composed of pulmonary endothelial cells (ECs), from rats of LPAL-2w and -5ws groups, which can be transcriptionally regulated by RELA (p65) and contributes to the lung inflammation. Conclusion and Implications: Our results suggested the upregulation of Piezo1 in both PASMCs and ECs, coordinate together and contribute to the pulmonary vascular remodeling and dysfunction in LPAL-PH rats, providing novel insights into the cell type-specific effects of Piezo1 in the pulmonary vasculature during high flow-related PH.

Metadynamics simulation has been used to describe the conformational energy landscapes of several helical quinoline oligoamides bearing β-pinene-derived pyridine at either the C or N terminus. Based on the experimental results, helix-sense preference for four types of foldamers with the chiral terminal group has been verified. To compare to the key factors of inducing handedness to helical-sense preference, a terminal group with three hydrogen bond sites is designed and corresponding foldamers are built. The calculated results show the delocalization effect and steric hindrance mainly responsible for a particular helix-sense preference for the investigated foldamers. The more hydrogen bonds between the terminal group and oligoamide units are formed, the more stable foldamers are.

long-term survival after lung transplantation has increased over recent years, but still fall short of providing extensive life expectancy for more than 10 years.

Detailed theoretical investigations on their structural and electronic properties of two-dimensional (2D) monofluorinating phenethylammonium perovskite are required to deeply understand the origin of the crystal structural and optoelectronic differences caused by organic spacers. Herein, formation energy, non-covalent interaction, band structure, exciton binding energy, carrier mobility and optical absorption spectra of 2D monofluorinating phenethylammonium lead iodide perovskite were calculated using density functional theory. Results show that steric effect leads to the orientational disorder of spacers in ortho-fluorinating phenethylammonium perovskite and weak interaction leads to the herringbone configuration of spacers in meta-fluorinating phenethylammonium perovskite. Exciton binding energy significantly influences the short circuit current density (JSC) of fluorophenethylammonium-based 2D perovskites, which can well explain the experimental trends of JSC. Formation energy analysis of perovskites with the same chemical components but different crystal structures and exciton binding energy calculation can be additional strategies in high-throughput screening for high-performance 2D perovskites.

The gut microbiota of bees affect nutrition, immunity, and host fitness, yet the role of diet, sociality, and geographic variation in determining microbiome structure, including strain-level diversity and relatedness, remain poorly understood. Here, we use full-length 16S amplicon sequencing to compare the crop and gut microbiomes of two incipiently social carpenter bee species, Xylocopa sonorina and Xylocopa tabaniformis, from multiple geographic sites within each species’ range. We found that Xylocopa species share a set of core taxa consisting of Bombilactobacillus, Bombiscardovia, and Lactobacillus apis, found in >95% of all individual bees sampled, and Gilliamella and Apibacter were also detected in the gut of both species with high frequency. The crop bacterial community of both species was comprised nearly entirely of Apilactobacillus with occasionally abundant nectar bacteria. Despite sharing core taxa, Xylocopa species’ microbiomes were distinguished by multiple bacterial lineages, including species-specific strains of core taxa. In both bee species, bacterial species exhibited geographic patterns in the presence of specific sequence variants. The use of long-read amplicons revealed otherwise cryptic species and population-level differentiation in core microbiome members which was masked when a shorter fragment of the 16S (V4) was considered. We conclude that these Xylocopa species host a distinctive microbiome, similar to that of previously characterized social apids, which suggests that further investigation to understand the evolution of bee microbiome and its drivers is warranted.

Background: Pediatric bronchoscopy is an important tool in pediatric pulmonology. However, the practices involved in the procedure are variable. Objective: To evaluate prevalent practice and variations in pediatric flexible bronchoscopy in India. Methods: An online survey conducted between September 2018 to March 2019 via Google forms. The survey was sent to members of the Respiratory Chapter of IAP, personal contacts, and members of Indian Chest Society. Physicians performing flexible bronchoscopy in children were asked to respond. Survey had 95 questions in seven domains including patient preparation, sedation, procedural aspects, monitoring, bronchoscope cleaning, and complications. Results: The survey received 24 (14 in private sector) complete responses from 14 cities. Pediatric bronchoscopy was mainly done for diagnostic purposes. Conscious sedation was used by most (19, 79%). Midazolam plus fentanyl 9 (37.5%) was the preferred sedation regimen. Routine atropine was used by 4 (16%). For topical anaesthesia- nebulized only, both nebulized and spray as go, and spray as go lignocaine only was used by 1 (4.2%), 6 (25%), and 17 (71%) centres, respectively. The methods of providing oxygen during bronchoscopy were free flow (9,37.5%), nasal prongs (8,33.3%), mask (6,25%), and LMA (1,4.2%). Therapeutic procedures included removal of mucus plugs (17, 71%), bronchoscopic intubation (11, 45%) and foreign body removal (10, 41%). The suction for BAL included wall mounted suction in maximum (15, 62.5%). The number of aliquots for BAL varied from 2-6 and volume for each aliquot also varied (1-2 ml/kg or 5-10 ml). The complications rate of less than 5 % was reported by almost all. Conclusion: There is large variation in pediatric flexible bronchoscopy practices across the country highlighting the need to develop a uniform guideline.

A first principle investigation of structural, mechanical, thermodynamical, electronic and thermoelectric properties of PdTiZ (Z = Ge and Pb) was carried out using plane wave pseudopotential (PP-PW) method. The exchange-correlation was considered with the generalized gradient approximation of Perdew-Burke-Ernzerhof (PBE-GGA). The energy band structure of the sample material exhibited semiconducting energy band structure with indirect energy band gaps of 0.66 eV and 0.387 eV in PdTiGe and PdTiPb respectively with density of states being mainly dominated by the p state of Z and d states of Ti atom around the vicinity of the Fermi energy level. The sample compounds were found to be mechanically stable in their non-magnetic cubic phase. PdTiGe was found to be harder and stiffer than PdTiPb. The positive phonon modes of the compounds predicted their dynamical stabilities. Thermodynamic study revealed that pressure has a negative effect on heat capacity whereas Debye temperature increases with enhanced pressure in both the sample compounds. The thermoelectric properties of the sample compounds predicted that p-type nature of the sample compounds possess better thermoelectric performance. The room temperature Seebeck coefficient values are found to be 98.73 µV/K and 94.82 µV/K for PdTiGe and PdTiPb, respectively, whereas they reflected the S values of 245.73 µV/K and 218.77 µV/K at 1200 K at n = 1021 cm-3. The lowest value of lattice thermal conductivity (K_L) of 2.28 W/m-K and 0.98 W/m-K was observed for PdTiGe and PdTiPb respectively. The optimum dimensionless figure of merit of 0.66 (1200 K) and 0.64 (1000 K) were found for p-type PdTiGe and PdTiPb, respectively at optimum carrier concentration.

Left ventricular non-compaction (LVNC) cardiomyopathy is an uncommon unclassified or genetic myocardial disorder. Frequent premature ventricular complexes (PVCs) as unique finding in LVNC cardiomyopathy are rare. We report a case of a 36-year-old woman in whom isolated LVNC was diagnosed due to an incidental finding of PVCs in pre-operative consultation.

Today, pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer, is one of the deadliest cancer types and remains largely unresolved. Through my research, I engineer a class of novel small molecule ligands to cure the disease by inhibiting its central carcinogenic pathway, taking the unique approach of applying the framework of targeted drug therapy and leveraging computer-aided techniques. The target molecule for which drug design is employed is xCT, a protein embedded in the ductal cell membrane that enables cancer cells to survive without a nutrient supply and kills normal cells of the pancreas. All viable drug candidate ligands must be engineered to have a complementary structure and biochemistry to the binding site of xCT. Starting with some known ligands of xCT to first identify the binding site and binding mode, I conduct guided substituent recombination based on the analysis of hydrophobicity and Coulombic surfaces as well as intermolecular interactions through computational docking simulations. In doing so, I employ industry-grade softwares including Chimera (to visualize 3D structures), Avogadro (to minimize free energies and infer 3D chemical structures), ChemDraw (to draw 2D chemical structures), AutoDockTools (to visualize the location of the binding site), AutoDock Vina (to perform docking simulations), and the SeaWulf computational cluster (for intensive, high accuracy computations). A total of 1461 novel results are tabulated, and the top two drug candidates among them are found to be CID 136204070 and 135564873, the best one among them CID 135564873. These can be used by drug industries to create new targeted drug therapies for pancreatic cancer, increasing the survival rate of the disease and saving countless lives through proactive treatment despite diagnostic delays. I've computationally ensured the absorption, distribution, metabolism, excretion, and toxicity results for the final drug candidates, and all of the relevant quantities are computationally verified through well-defined biochemistry lab procedures for the final ligand molecules and found to be very reliable for drug candidacy. I did this project through the Simons Summer Research Program at Stony Brook University as a Simons Fellow and paid research intern, under the guidance of Distinguished Professor Iwao Ojima and student mentors Adam Taouil and Frank Wang.

As a new type of gas-liquid microreactors, the gas-liquid mini-bubble column have potential applications. However, few studies on the flow fields in the mini-bubble column can be found at present. In this work, Particle Image Velocimetry (PIV) was first used to visually study the velocity fields, vorticity fields and bubble dynamics in the gas-liquid mini-bubble columns with column inner diameters of 1to 3 mm and mini-bubble diameters ranged from 0.7 to 1.3 mm. It is found that with the increase of superficial liquid velocity, bubbles rose from almost straight line to Z-shaped or S-shaped trajectory, and the bubble trajectory changed from 1-D to 3-D; when the bubble velocity changed, the bubble size and gas holdup decreased; bubble terminal velocity was controlled by bubble buoyancy and flow resistance, and increased slightly with bubble coalescence. These findings may provide basic reference for the design and scale-up of such mini-bubble column reactor.

Background: In this pilot study, we investigated whether induced sputum (IS) could serve as a viable alternative to bronchoalveolar lavage (BAL) and yield robust inflammatory biomarkers in toddlers with cystic fibrosis (CF) featuring minimal structural lung disease. Methods: We collected IS, BAL (right middle lobe and lingula) and blood, and performed chest computed tomography (CT) scans from 2-year-olds with CF (N=11), all within a single visit. Inflammatory biomarkers included 20 soluble immune mediators and neutrophil elastase (NE), as well as frequency and phenotype of T cells, monocytes / macrophages and neutrophils. Results: At the molecular level, nine mediators showed similar levels in IS and BAL (CXCL1, CXCL8, IL-1, IL-1RA, IL-6, CCL2, CXCL10, M-CSF, VEGF-A), four were higher in IS than in BAL (CXCL5, IL-1, CXCL11, TNFSF10) and two were present in IS but undetectable in BAL (IL-10, IFN-). Meanwhile, soluble NE had lower activity in IS than in BAL. At the cellular level, T-cell frequency was lower in IS than in BAL. Monocytes / macrophages were dominant in IS and BAL with similar frequencies but differing expression of CD16 (lower in IS), CD115 and surface-associated NE (higher in IS). Neutrophil frequency and phenotype did not differ between IS and BAL. Conclusions: IS collected from 2-year-olds with CF yields biomarkers of early airway inflammation with good agreement with BAL notably with regards to molecular and cellular outcomes related to neutrophils and monocytes/macrophages.

How the environment impacts the assembly of local communities as well as their spatial and temporal connection in a metacommunity has remained a largely unresolved question in community ecology. This study aims to unravel the underlying metacommunity dynamics and environmental factors that result in observed zooplankton communities. In extension to most studies concerning metacommunity dynamics, we jointly examine zooplankton communities both in open water and in the sediment where zooplankton resting stages/dormant communities are stored. We used a two-fragment DNA metabarcoding approach (COI and 18S) to monitor zooplankton communities of 24 kettle holes over a two-year period to unravel (I) how the community is spatially and temporally connected, (II) what are the environmental factors influencing local communities, and (III) what are the underlying metacommunity dynamics in this system. We found a strong separation of zooplankton communities from kettle holes of different hydroperiods (ephemeral vs. permanent) throughout the season, while the community composition within single kettle holes did not differ between years. Species richness was primarily dependent on pH and hydroperiod, while species diversity was influenced by kettle hole location. Community composition was further impacted by kettle hole size, water temperature and pH. Soil samples showed a separate community composition compared to water samples, but did not differ between ephemeral and permanent kettle holes. Our results suggest that communities are mainly structured by environmental filtering based on pH, water temperature, kettle hole size and hydroperiod. Species sorting is a dominant driver in community assembly in the studied kettle hole zooplankton metacommunity.

We report a new case of chronic recurrent annular neutrophilic dermatosis in a woman. Through our observation, we aim to make the clinician aware of this rare entity, in order to consider it among the diagnostic hypotheses of annular dermatosis, with centrifugal, recurrent and chronic evolution.

Nowadays, patient-centred practice represents the key for quality and successful outcomes in healthcare. At the same time, shared decision-making is acknowledged as the highlight of patient-centred care. Informed consent, whenever derives appropriately from a two-way communication between doctor and patient, follows a negotiation process that leads to appropriate and shared decisions. This article aims to show how the typical negotiating styles can lead or not to effective informed consent and conflict mediation processes. To this end, the three negotiating styles currently theorized (sharks, saints, and samurai) are integrated into the three clinical models of doctor-patient interaction (paternalistic, interpretative and autonomist). Currently, being any paternalistic attitude disapproved both ethically and legally, the model of autonomy is the only suitable one to communicate effectively. A concrete case from cardiology is reported to show the different negotiation styles within a doctor-patient conversation. Upstream, drawing inspiration from the samurai negotiating style, the doctor could find a new approach to effective informed consent. Downstream, during mediation, he/she could recompose all those conflicts that stem from an unsatisfying relationship with the patient. These results suggest, finally, that the physicians should be aware of their own prevalent negotiating style and of how to improve it if necessary.

Benzalkonium chloride (BAC) is a quaternary ammonium compound commonly employed as a preservative in several multidose eye drops. Its use is associated with several adverse events, particularly when used chronically. Topically instilled BAC acts not only on superficial structures but also reaches deeper tissues (trabecular meshwork, optic nerve) and can be deleterious in patient under chronic treatment. In glaucomatous patients, BAC is the primary cause of ocular surface disease (OSD), and it can lead to significant morbidity, influence treatment compliance, quality of life, and surgical outcomes. Clinical and experimental evidence demonstrates that BAC causes instability of the tear layer, loss of goblet cells, apoptosis, subclinical neuroinflammation, and antibiotic resistance. Considering the validity of the alternative formulations (alternative preservatives or preservative-free formulations) it is unreasonable to persist in using such toxic compounds and, perhaps it is time for a moratorium on the use of BAC in eye drops.