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Transcatheter mitral valve-in-valve implantation is a preferred treatment for degenerating mitral bioprosthetic valves in high-risk surgical patients. A balloon-expandable transcatheter heart valve delivered through a postero-inferior transseptal puncture is deployed within the prosthesis over a guidewire secured in the left ventricle. Patients with aneurysmal left atrium and altered angulation between the planes of atrial septum and mitral prosthesis have unstable position of the guidewire that flips out of the left ventricle into the left atrium when the valve delivery system is advanced. Instead of a transapical access to snare the guidewire and create a railroad in such instances, we report a new technique of transarterial retrograde snaring of the guidewire in the left ventricle for stabilization., (© 2024 Wiley Periodicals LLC.)

Isophorone is a cyclic ketone that has gained significant attention in the field of organic chemistry due to its versatile reactivity and structural attributes. Derivatives of isophorone offer a broad spectrum of applications ranging from pharmaceuticals to polymer chemistry. With the aim of developing novel hybrid structures based on benzylidene by combining with isophorone scaffold, we report 3 derivatives of the benzylidene-isophorone hybrids and its potent anticancer activity. In order to optimize the anticancer activity of hybrids di-substitution of -Cl group in C 2 and C 6 position of phenyl ring (compound1), -OCH 3 group in C 2 and C 5 position of phenyl ring (compound2), and -OCH 3 group in C 2 and C 3 position of phenyl ring (compound3) of benzylidene (PhCH=) moiety were made. The structure of Compounds1,2 and 3 were elucidated using spectral and XRD methods. Compounds1,2 and 3 exhibit space group P c a 21, P-1, and P 1 21/n 1 respectively. Compounds1,2 and 3 were tested for the potent anticancer activity on MDA MB-231 cell line. All the three compounds exhibit good anticancer activity on the breast cancer cells. The parent hybrid with ortho, ortho directing -Cl (1) exhibits strong antiproliferation effect (IC 50  = 0.028 µM) on MDA-MB 231 cell line. However, hybrid structures with ortho, meta directing -OCH 3 (2) group showed moderate effect (IC 50  = 0.061 µM) and hybrid with ortho, meta directing -OCH 3 (3) substitution showed the least potent anticancer activity (IC 50  = 0.074 µM). The benzylidene-isophorone hybrids exhibit anticancer effects in the following order: 1 > 2 > 3., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: When young patients with an oval fossa defect present early with symptoms of heart failure and pulmonary hypertension, surgical treatment is recommended in small bodyweight rather than transcatheter closure., Methods: Outcomes of device closure in consecutive symptomatic children weighing under 10 kg were compared with young children aged below 4 years but weighing above 10 kg. Transthoracic echocardiography under conscious sedation guided the procedure in all without need for balloon sizing, transesophageal echocardiogram, and intubation anaesthesia. Symptoms, anthropometry, shunt ratio, pulmonary pressures, defect and device size, percentage oversizing, device/body weight ratio, complications, and post-procedural growth spurt were compared., Results: Ninety-six patients weighing under 10 kg were compared with 160 patients weighing above 10 kg. In total, 83.3% of patients in the study group and 25% of controls were severely malnourished. The median indexed defect size was 35.2 mm/sq.m and 27.4 mm/sq.m, and the device was oversized by 8.7% and 14.2% in the study group and controls, respectively. The device/body weight ratio was 1.93 in study group and 1.4 in controls. Procedure was successful in all except one patient weighing under 10 kg who had a device embolisation. Both groups showed significant growth spurts and proportion, with severe malnutrition reduced to 42% and 11% in the two groups., Conclusions: Device closure was feasible and safe in patients under 10 kg. Transthoracic echocardiographic imaging on conscious sedation provided adequate guidance. Symptoms and growth significantly improved after intervention. Despite a larger defect size, smaller patients had comparable outcomes. In symptomatic children under 10 kg needing early closure, transcatheter intervention should not be deferred.

Virtualization is the process of sharing physical machine resources into multiple Virtual Machines (VMs) for the effective utilization of resources. The major issues are in handling physical resources such as high demand of resources, infrastructure issues and operational issues. Also violating Service Level Agreement (SLA) is another problem to lead the violations. In this case, VM consolidation method is used to migrate the VMs and optimize the efficient way to use the resources. So we get minimized energy consumptions. Existing methods has increased energy consumption and overhead issues. In this paper we propose adaptive backtracking methods to provide VM consolidation based on less energy consumptions. We use Adaptive Hill Climbing and Pursuit algorithms to consolidate the VMs and use the VMs with efficient energy consumption. We implement this simulations using Matlab in Hybrid Cloud Environment. The performance factors are obtained with less energy consumption and compare the results with existing methods. Overall our proposed system is achieving 95% of accuracy index with lower energy consumption such as 28%, 30% and 32% with multiple VMs consolidations., (© 2024. The Author(s).)

Addison's disease (AD), or primary adrenal insufficiency, was first described by Thomas Addison in patients with adrenal tuberculosis (TB). Over the past several decades, along with the introduction of antituberculous treatment (ATT), the incidence of both has declined. The most common symptoms are nonspecific, leading to delayed diagnosis; patients may first present with a life-threatening crisis. Here, we report a case of AD that, upon further workup, was found to be due to one of the most common infections in India-TB., (© Journal of the Association of Physicians of India 2024.)

Herein, the interaction of an antidiabetic drug, metformin hydrochloride (MHCl), and a cationic surfactant, cetylpyridinium bromide (CPB) is investigated in an aqueous medium. The critical micellar concentration (CMC) of CPB is estimated through conductivity experiments and found to be reduced on adding MHCl and further decreased in the presence of NaCl. The reduced CMC is attributed to the solubilization of MHCl by CPB through micellization and the micellization is found to be thermodynamically spontaneous that experiences an augmentation in the presence of NaCl. This is identified from the negative value of standard free energy ( Δ G 0 m ). The higher negative value of Δ G 0 m (-55.41 kJ mol -1 ) for CPB + MHCl + NaCl than CPB (-37.89 kJ mol -1 ) and CPB + MHCl (-34.08 kJ mol -1 ) is suggestive of the above phenomenon. The positive values of Δ S 0 m in all three cases confirm that the micellization is entropy driven. The binding of MHCl on CPB is quantified by estimating binding constant using the Benesi-Hildebrand (B-H) plot through UV-visible spectral methods. The binding constant values were calculated to be 2.70 M -1 for CPB + MHCl + NaCl compared to 1.258 M -1 for CPB + MHCl predicting a favoring of micellization in the presence of NaCl which is higher than that in the presence of co-solvents. The molecular interaction of MHCl and CPB is justified using FT-IR and NMR techniques. The surface properties of drug surfactant interactions are assessed using SEM techniques. The point of interaction between the drug and surfactant is visualized through the molecular docking approach. The results suggest that CPB would be an effective solubilizer for developing MHCl drug formulations.Communicated by Ramaswamy H. Sarma.

The role of striatal pathways in cognitive processing is unclear. We studied dorsomedial striatal cognitive processing during interval timing, an elementary cognitive task that requires mice to estimate intervals of several seconds and involves working memory for temporal rules as well as attention to the passage of time. We harnessed optogenetic tagging to record from striatal D2-dopamine receptor-expressing medium spiny neurons (D2-MSNs) in the indirect pathway and from D1-dopamine receptor-expressing MSNs (D1-MSNs) in the direct pathway. We found that D2-MSNs and D1-MSNs exhibited distinct dynamics over temporal intervals as quantified by principal component analyses and trial-by-trial generalized linear models. MSN recordings helped construct and constrain a four-parameter drift-diffusion computational model. This model predicted that disrupting either D2-MSNs or D1-MSNs would increase interval timing response times and alter MSN firing. In line with this prediction, we found that optogenetic inhibition or pharmacological disruption of either D2-MSNs or D1-MSNs increased interval timing response times. Pharmacologically disrupting D2-MSNs or D1-MSNs also changed MSN dynamics and degraded trial-by-trial temporal decoding. Together, our findings demonstrate that D2-MSNs and D1-MSNs make complementary contributions to interval timing despite opposing dynamics, implying that striatal direct and indirect pathways work together to shape temporal control of action. These data provide novel insight into basal ganglia cognitive operations beyond movement and have implications for human striatal diseases and therapies targeting striatal pathways.

Oral squamous cell carcinoma (OSCC) is the most common of all head and neck cancers accounting for 90% of all oral malignancies. It is commonly associated with the use of tobacco smoking or quid form. The incidence of oral carcinoma is higher in males than females with a ratio of 1.4:1, though females commonly adopt tobacco quid chewing habit. OSCC metastasis to cervical lymph node at the rate of 20-42.6% according to studies reported so far. Papillary thyroid carcinoma (PTC) occurs with a higher incidence in females than males with metastasis into cervical lymph nodes though the primary lesion frequently goes undetected. Concurrent metastasis of OSCC and PTC to the cervical lymph node during neck dissection has been reported rarely in the literature. This case report presents a 48-year-old female with lymph node metastasis of carcinoma of the right mandibular posterior alveolar region concurrently with metastasis of PTC (with primary lesion clinically undetected) encountered during cervical lymph node examination., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Baskaran et al.)

In the title compound, C 31 H 28 O 4 , the phenyl rings of the chalcone unit subtend a dihedral angle of 26.43 (10)°. The phenyl rings of the pendant benz-yloxy groups are orientated at 75.57 (13) and 75.70 (10)° with respect to their attached ring. In the crystal, weak C-H⋯O and C-H⋯π inter-actions link the mol-ecules. The inter-molecular inter-actions were qu-anti-fied and analysed using Hirshfeld surface analysis, which showed a breakdown into H⋯H (49.8%), H⋯C/C⋯H (33.8%) and H⋯O/O⋯H (13.6%) inter-actions with other types making negligible contributions., (© Jeyashri et al. 2024.)

Background: Microcrystalline cellulose (MCC) is a novel organic material developed by one of the authors in this study. When MCC was incorporated with conventionally available denture base resin, it demonstrated increased flexural strength and flexural modulus. However, it was speculated that because the material is organic, it can promote the growth of Candida . The purpose of this study is to evaluate the Candida albicans biofilm formation on polymethyl methacrylate (PMMA) denture base resin incorporated with MCC., Materials and Methods: MCC is an organic material extracted from the oil palm empty fruit bunch (OPEFB). The growth of C. albicans and biofilm formation in three test groups were compared by biofilm assay and imaging techniques like microscopy (by safranin staining) and scanning electron microscopy. The three test groups were comprised of MCC-reinforced PMMA containing OPEFB fibers of 50-micrometer thickness at 5% weight reinforcement, conventionally and commercially available heat cure PMMA, and an empty well to assess any discrepancies from the environment., Results: The test groups showed increased biofilm formation by C. albicans compared to commercially and conventionally available heat cure PMMA. Reinforcement with MCC showed higher biofilm formation of 1.43 times higher compared to conventional PMMA. Biofilms formed by Candida albicans on MCC-reinforced PMMA appeared heterogeneous in structure, comprised of yeast cells and hyphae, surrounded by a higher density of polysaccharide extracellular matrix material compared to that of conventionally available heat cure PMMA., Conclusion: Biofilm formation is increased in denture base resin incorporated with MCC. More investigation is warranted to study the antifungal efficacy of the addition of antifungal agents to the reinforced denture base resin., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, S et al.)

Superior sinus venosus defects (SVD) are interatrial communications located above the confines of the oval fossa, where unroofing of the right upper pulmonary vein leads to its anomalous drainage to the superior venacava. Recent emergence of transcatheter closure of these defects using covered stents is an attractive alternative option especially in adults with additional comorbidities. This article focuses on various aspects of non-surgical closure of SVD, including patient selection, appropriate hardware options, step-by-step procedural details, evolution and modifications in the techniques over the last decade, protocols for follow-up evaluation, and potential complications associated with this intervention., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Indian coastal waters are critical for dugong populations in the western Indian Ocean. Systematic spatial planning of dugong habitats can help to achieve biodiversity conservation and area-based protection targets in the region. In this study, we employed environmental niche modelling to predict suitable dugong habitats and identify influencing factors along its entire distribution range in Indian waters. We examined data on fishing pressures collected through systematic interview surveys, citizen-science data, and field surveys to demarcate dugong habitats with varying risks. Seagrass presence was the primary factor in determining dugong habitat suitability across the study sites. Other variables such as depth, bathymetric slope, and Euclidean distance from the shore were significant factors, particularly in predicting seasonal suitability. Predicted suitable habitats showed a remarkable shift from pre-monsoon in Palk Bay to post-monsoon in the Gulf of Mannar, indicating the potential of seasonal dugong movement. The entire coastline along the Palk Bay-Gulf of Mannar region was observed to be at high to moderate risk, including the Gulf of Mannar Marine National Park, a high-risk area. The Andaman Islands exhibited high suitability during pre- and post-monsoon season, whereas the Nicobar Islands were highly suitable for monsoon season. Risk assessment of modelled suitable areas revealed that < 15% of high-risk areas across Andaman and Nicobar Islands and Palk Bay and Gulf of Mannar, Tamil Nadu, fall within the existing protected areas. A few offshore reef islands are identified under high-risk zones in the Gulf of Kutch, Gujarat. We highlight the utility of citizen science and secondary data in performing large-scale spatial ecological analysis. Overall, identifying synoptic scale 'Critical Dugong Habitats' has positive implications for the country's progress towards achieving the global 30 × 30 target through systematic conservation planning., (© 2024. The Author(s).)

Background: Transcatheter correction of sinus venosus defects (SVDs) using balloon-mounted covered stents provides an attractive surgical alternative. Surgery may be complicated by superior vena caval or right upper pulmonary vein (RUPV) stenosis, sinus nodal dysfunction, and residual additional pulmonary veins., Objectives: Being a new intervention, technical modifications would simplify the procedure, improve universal applicability, and reduce or tackle complications., Methods: Patients were included if balloon interrogation of cavoatrial junction confirmed closure of SVD and redirected RUPV to the left atrium. A single-center experience was analyzed to summarize the procedural modifications over 8 years. Transesophageal echocardiogram (TEE) on follow-up was done to identify residual shunt, RUPV flows, and stent thrombosis., Results: A total of 100 patients including 9 children with a median age of 35 years (range, 4-69 years) underwent SVD closure after balloon interrogation. Among 57 patients balloon interrogated in the first 5 years, 70% underwent transcatheter closure, with 2 failures. RUPV occlusion caused the exclusions. Inclusions improved to 94% among the subsequent 65 balloon interrogations when RUPV protection was implemented, with 1 failure. Stent embolization caused the 3 failures warranting surgery. Recent modifications included limited transesophageal echocardiogram without anesthesia, avoiding venovenous circuit, interrogation with semicompliant balloons, trans-septal RUPV protection, overlapping stents to permit additional vein drainage to superior vena cava and tackle embolizations. There were no deaths. Minor complications included stent embolizations stabilized in catheterization laboratory in 2 patients, left innominate vein jailing in 2 patients, insignificant residual flows, and nonocclusive asymptomatic stent thrombosis in 4 patients., Conclusions: Procedural success was 97%. Recent modifications increased patient inclusions, decreased complications, and simplified the intervention., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: To characterize the diagnosis, frequency, and procedural implications of septal venous channel perforation during left bundle branch area pacing (LBBAP)., Methods and Results: All consecutive patients undergoing LBBAP over an 8-month period were prospectively studied. During lead placement, obligatory septal contrast injection was performed twice, at initiation (implant entry zone) and at completion (fixation zone). An intuitive fluoroscopic schema using orthogonal views (left anterior oblique/right anterior oblique) and familiar landmarks is described. Using this, we resolved zonal distribution (I-VI) of lead position on the ventricular septum and its angulation (post-fixation angle θ). Subjects with and without septal venous channel perforation were compared. Sixty-one patients {male 57.3%, median age [interquartile range (IQR)] 69.5 [62.5-74.5] years} were enrolled. Septal venous channel perforation was observed in eight (13.1%) patients [male 28.5%, median age (IQR) 64 (50-75) years]. They had higher frequency of (i) right-sided implant (25% vs. 1.9%, P = 0.04), (ii) fixation in zone III at the mid-superior septum (75% vs. 28.3%, P = 0.04), (iii) steeper angle of fixation-median θ (IQR) [19 (10-30)° vs. 5 (4-19)°, P = 0.01], and (iv) longer median penetrated-lead length (IQR) [13 (10-14.8) vs. 10 (8.5-12.5) mm, P = 0.03]. Coronary sinus drainage of contrast was noted in five (62.5%) patients. Abnormal impedance drops during implantation (12.5% vs. 5.7%, P = NS) were not significantly different., Conclusion: When evaluated systematically, septal venous channel perforation may be encountered commonly after LBBAP. The fiducial reference framework described using fluoroscopic imaging identified salient associated findings. This may be addressed with lead repositioning to a more inferior location and is not associated with adverse consequence acutely or in early follow-up., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This study aimed to evaluate the current state of congenital interventional cardiology training worldwide, with a focus on case volumes, competency assessment, and the need for ongoing mentorship during early career stages. A survey was conducted among program directors (PDs) of congenital interventional training programs across the globe. The survey gathered data on training pathways, case volumes, types of procedures performed, trainee competency assessment, and the role of ongoing mentorship. Of the 79 PDs who completed the survey, it was observed that training pathways and case volumes varied significantly, particularly between the United States and other countries. Most PDs reported an annual laboratory case volume of >500 congenital cardiac cases, with most cases being interventional. While trainees demonstrated competency in simple procedures (diagnostic cases, simple ASD closure), complex interventions (such as patent ductus arteriosus closure in premature infants) require ongoing mentorship for graduates. PDs recommended a minimum case volume of 400 total cases for trainees, including 250 interventional cases. In addition to case volumes, assessing trainee competency was deemed important, with clinical reasoning, judgment, skillset, teamwork, and complication management being key areas of evaluation. The study highlights the variability in congenital interventional cardiology training and the need for ongoing mentorship during the early career years. External mentorship programs, facilitated by national and international societies, are proposed to provide critical support for early career interventionalists thus enhancing patient care for congenital heart disease. Ultimately, the findings of this survey may serve as a framework for future training standards and guidelines in this specialized field., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We investigated the angiogenesis-modulating ability of noscapine in vitro using osteosarcoma cell line (MG-63) and in vivo using a zebrafish model. MTT assay and the scratch wound healing assay were performed on the osteosarcoma cell line (MG-63) to analyze the cytotoxic effect and antimigrative ability of noscapine, respectively. We also observed the antiangiogenic ability of noscapine on zebrafish embryos by analyzing the blood vessels namely the dorsal aorta, and intersegmental vessels development at 24, 48, and 72 h postfertilization. Real-time polymerase chain reaction was used to analyze the hypoxia signaling molecules' gene expression in MG-63 cells and zebrafish embryos. The findings from the scratch wound healing demonstrated that noscapine stopped MG-63 cancer cells from migrating under both hypoxia and normoxia. Blood vessel development and the heart rate in zebrafish embryos were significantly reduced by noscapine under both hypoxia and normoxia which showed the hemodynamics impact of noscapine. Noscapine also downregulated the cobalt chloride (CoCl 2 ) induced hypoxic signaling molecules' gene expression in MG-63 cells and zebrafish embryos. Therefore, noscapine may prevent MG-63 cancer cells from proliferating and migrating, as well as decrease the formation of new vessels and the production of growth factors linked to angiogenesis in vivo under both normoxic and hypoxic conditions., (© 2024 Wiley Periodicals LLC.)

Our investigation revealed that alterations in sulphur (S) pools are predominantly governed by soil organic carbon (SOC), soil nitrogen (N), microbial biomass, and soil enzyme activities in sandy clay loam (Vertic Ustropept) soil. We employed ten sets of nutrient management techniques, ranging from suboptimal (50% RDF) to super-optimal doses (150% RDF), including NPK + Zn, NP, N alone, S-free NPK fertilizers, NPK + FYM, and control treatments, to examine the interrelation of S with SOC characteristics. Fourier-transform infrared (FT-IR) spectroscopy was utilized to analyze the functional groups present in SOC characterization across four treatments: 100% NPK, 150% NPK, NPK + FYM, and absolute control plots. Principal component analysis (PCA) was then applied to assess 29 minimal datasets, aiming to pinpoint specific soil characteristics influencing S transformation. In an Inceptisol, the application of fertilizers (100% RDF) in conjunction with 10 t ha -1 of FYM resulted in an increase of S pools from the surface to the subsurface stratum (OS > HSS > SO 4 2- -S > WSS), along with an increase in soil N and SOC. FT-IR spectroscopy identified cellulose and thiocyanate functional groups in all four plots, with a pronounced presence of carbohydrate-protein polyphenol, sulfoxide (S=O), and nitrate groups specifically observed in the INM plot. The PCA findings indicated that the primary factors influencing soil quality and crop productivity (r 2 of 0.69) are SOC, SMBC, SMBN, SMBS, and the enzyme activity of URE, DHA, and AS. According to the study, the combined application of fertilizer and FYM (10 t ha -1 ) together exert a positive impact on sulphur transformation, SOC accumulation, and maize yield in sandy clay loam soil., (© 2024. The Author(s).)

Social-educational robotics, such as NAO humanoid robots with social, anthropomorphic, humanlike features, are tools for learning, education, and addressing developmental disorders (e.g., autism spectrum disorder or ASD) through social and collaborative robotic interactions and interventions. There are significant gaps at the intersection of social robotics and autism research dealing with how robotic technology helps ASD individuals with their social, emotional, and communication needs, and supports teachers who engage with ASD students. This research aims to (a) obtain new scientific knowledge on social-educational robotics by exploring the usage of social robots (especially humanoids) and robotic interventions with ASD students at high schools through an ASD student-teacher co-working with social robot-social robotic interactions triad framework; (b) utilize Business Model Canvas (BMC) methodology for robot design and curriculum development targeted at ASD students; and (c) connect interdisciplinary areas of consumer behavior research, social robotics, and human-robot interaction using customer discovery interviews for bridging the gap between academic research on social robotics on the one hand, and industry development and customers on the other. The customer discovery process in this research results in eight core research propositions delineating the contexts that enable a higher quality learning environment corresponding with ASD students' learning requirements through the use of social robots and preparing them for future learning and workforce environments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Arora, Arora, Sivakumar and McIntyre.)

Background: Generalized myasthenia gravis (gMG) is a chronic, unpredictable disease associated with high treatment and disease burdens, with a need for more effective and well-tolerated treatments., Objectives: To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population., Design: Ongoing, multicenter, phase III open-label extension (OLE) study., Methods: Eligible patients had completed a qualifying randomized, placebo-controlled phase II or phase III zilucoplan study and received daily, self-administered subcutaneous 0.3 mg/kg zilucoplan. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score., Results: In total, 200 patients enrolled. At the cut-off date (8 September 2022), median (range) exposure to zilucoplan in RAISE-XT was 1.2 (0.11-4.45) years. Mean age at OLE baseline was 53.3 years. A total of 188 (94%) patients experienced a TEAE, with the most common being MG worsening ( n  = 52, 26%) and COVID-19 ( n  = 49, 25%). In patients who received zilucoplan 0.3 mg/kg in the parent study, further improvements in MG-ADL score continued through to Week 24 (least squares mean change [95% confidence interval] from double-blind baseline -6.06 [-7.09, -5.03]) and were sustained through to Week 60 (-6.04 [-7.21, -4.87]). In patients who switched from placebo in the parent study, rapid improvements in MG-ADL score were observed at the first week after switching to zilucoplan; further improvements were observed at Week 24, 12 weeks after switching (-6.46 [-8.19, -4.72]), and were sustained through to Week 60 (-6.51 [-8.37, -4.65]). Consistent results were observed in other efficacy endpoints., Conclusion: Zilucoplan demonstrated a favorable long-term safety profile, good tolerability, and sustained efficacy through to Week 60 with consistent benefits in a broad AChR+ gMG population. Additional long-term data will be available in future analyses., Trial Registration: ClinicalTrials.gov identifier: NCT04225871 (https://clinicaltrials.gov/ct2/show/NCT04225871)., (© The Author(s), 2024.)

This study aims to investigate the pulmonary functions and respiratory symptoms of workers in the neem oil extraction industry in Tamil Nadu, India, who are exposed to neem oil dust and chemicalsin their occupational environment. Fifty male workers from the exposed group and 50 male workers from the non-exposed group to neem dust and chemicals were investigated for this study. A modified respiratory assessment questionnaire based on the American Thoracic Society (ATS) standard and portable hand-held spirometry were used to assess their respiratory symptoms and pulmonary function. Respiratory symptoms such as coughing, sneezing, wheezing, and, nasal irritation are found to be higher in the exposed groups than in the controlled groups. The pulmonary function of exposed workers had doubled respiratory problems than the controlled groups, which indicates the impacts of dust and chemicals generated during neem oil extraction on workers' health. Forced expiratory volume in one second (FEV 1 )/forced vital capacity FVC)% was noted regarding the duration of exposure to neem oil dust ( P < 0.001). Also, there was a high difference between the heavily exposed and the lightly exposed ( P < 0.001). Hence, to mitigate these problems, the oil mill workers should be cautious and wear personal protection equipment during working hours, and it is recommended to have an exhaust ventilation system., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Occupational and Environmental Medicine.)

Cipaglucosidase alfa plus miglustat (cipa + mig) is a novel, two-component therapy for Pompe disease. We report data from the Phase I/II ATB200-02 study for up to 48 months of treatment. Four adult cohorts, including one non-ambulatory ERT-experienced (n = 6) and three ambulatory cohorts, (two enzyme replacement therapy [ERT]-experienced cohorts [2-6 years (n = 11) and ≥ 7 years (n = 6)]), one ERT-naïve cohort (n = 6), received 20 mg/kg intravenous-infused cipa plus 260 mg oral mig biweekly. Change from baseline (CFBL) for multiple efficacy endpoints at 12, 24, 36, and 48 months, pharmacodynamics, pharmacokinetics, safety, and immunogenicity data were assessed. Six-minute walking distance (% predicted) improved at 12, 24, 36, and 48 months: pooled ambulatory ERT-experienced cohorts, mean(± standard deviation [SD]) CFBL: 6.1(± 7.84), n = 16; 5.4(± 10.56), n = 13; 3.4(± 14.66), n = 12; 5.9(± 17.36), n = 9, respectively; ERT-naïve cohort: 10.7(± 3.93), n = 6; 11.0(± 5.06), n = 6; 9.0(± 7.98), n = 5; 11.7(± 7.69), n = 4, respectively. Percent predicted forced vital capacity was generally stable in ERT-experienced cohorts, mean(± SD) CFBL - 1.2(± 5.95), n = 16; 1.0(± 7.96), n = 13; - 0.3(± 6.68), n = 10; 1.0(± 6.42), n = 6, respectively, and improved in the ERT-naïve cohort: 3.2(± 8.42), n = 6; 4.7(± 5.09), n = 6; 6.2(± 3.35), n = 5; 8.3(± 4.50), n = 4, respectively. Over 48 months, CK and Hex4 biomarkers improved in ambulatory cohorts. Overall, cipa + mig was well tolerated with a safety profile like alglucosidase alfa. ATB200-02 results show the potential benefits of cipa + mig as a long-term treatment option for Pompe disease. Trial registration number: NCT02675465 January 26, 2016., (© 2023. The Author(s).)

Surgical myectomy is recommended for symptomatic hypertrophic obstructive cardiomyopathy (HOCM) after optimal pharmacological therapy. Percutaneous transluminal septal myocardial ablation (PTSMA) is reserved for high-risk adults. Symptomatic patients below 25 years underwent either surgery or PTSMA after heart-team discussion and informed consent. Echocardiography assessed gradients in surgical group. PTSMA group underwent invasive transseptal hemodynamic assessment, selective coronary angiography and super-selective cannulation of septal perforators using microcatheters. Contrast echocardiography through the microcatheter identified the myocardial target for PTSMA. Hemodynamic and electrocardiographic monitoring guided alcohol injection. Both groups were continued on beta-blockers. Symptoms, echocardiographic gradients and Brain natriuretic peptide (NTproBNP) measurements were assessed on follow-up. Twelve patients aged 5-23 years (11-98 kg) formed the study group. Indications for PTSMA in 8 patients included abnormal mitral valve anatomy warranting replacement (n = 3), Jehovah's witness (n = 2), severe neurodevelopmental and growth retardation (n = 1) and refusal of surgery (n = 2). PTSMA targeted first perforator (n = 5), second perforator (n = 2) and anomalous septal artery from left main trunk (n = 1). Outflow gradient reduced from 92.5 ± 19.7 to 33.1 ± 13.5 mmHg. At a median follow-up of 38 months (range 3-120 weeks), the peak instantaneous echocardiographic gradient was 32 ± 16.5 mmHg. Gradient reduced in four surgical patients from 86.5 ± 16.3 mmHg to 42 ± 14.7 mm Hg. All patients were in NYHA class I/II on follow-up. The mean NTproBNP in PTSMA group reduced from 6084 ± 3628 pg/ml to 3081 ± 2019 pg/ml; it was 1396 and 1795 pg/ml in surgery. PTSMA may be considered in medically refractory high-risk young patients. It relieves symptoms and reduces gradient. Though surgery is preferred in young patients, PTSMA may have a role in selected patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Transcatheter closure of sinus venosus defect (SVD) is an emerging intervention that utilizes a covered stent to redirect the right upper pulmonary vein to the left atrium. Preprocedural computed tomography analysis, as well as the interventional procedure, necessitates the use of radiographic contrast media. Contrast use is prohibited in patients with advanced kidney disease, who also carry high surgical risks of cardiopulmonary bypass. Transesophageal echocardiography-guided catheter intervention with zero contrast use is presented in this report, along with technical details about planning the procedure. Covered stent exclusion of SVD without contrast use has not been reported in the literature so far., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Annals of Pediatric Cardiology.)

While infradiaphragmatic total anomalous pulmonary venous drainage to portal vein is well described, hemianomalous drainage of right pulmonary veins to portal vein in Scimitar syndrome has not yet been reported.

Background: Aortico right atrial tunnel (ARAT) is a rare extracardiac communication between the aorta and the right atrium with two anatomical types. A recent global review identified 59 patients., Methods: Patients with ARAT from two centers were analyzed for their demographics, symptoms, morphology, management, and follow-up thromboprophylaxis., Results: Among 21 patients including 8 males with a median age of 3 years (18 days-72 years) diagnosed as ARAT, 12 (57%) had posterior tunnels and 9 had anterior tunnels. Four patients had multiple exits. Eighteen tunnels were closed after arteriovenous circuit formation. Six patients (29%) weighing <10 kg presented early with heart failure. Transcatheter closure normalized the hemodynamics including in one infant after failed surgery. Two elderly patients (10%) above 60 years presented with angina and atrial fibrillation. The rest were asymptomatic. Occluders were positioned in the narrow proximal aortic end of the tunnel in all except two patients, where the distal atrial end was closed. All procedures were successful without complications. There was one late death after 1 year from subarachnoid hemorrhage. At a median follow-up of 96 months, all survivors were asymptomatic. Thromboprophylaxis with dual antiplatelets for 1-2 years followed earlier was recently changed to aspirin with Coumadin. Complete remodeling occurred when the proximal aortic end was closed, but partial persistence of the track was noted after distal closure., Conclusions: This largest cohort of ARAT showed the safety and efficacy of transcatheter closure even in neonates. The narrow proximal aortic end should be the target for closure rather than the distal atrial end to achieve complete remodeling., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Annals of Pediatric Cardiology.)

Transcatheter closure of superior vena cava (SVC) form of sinus venosus defects (SVDs) using covered stents is emerging as an alternative to surgery in the current decade. A covered stent placed in the cavoatrial junction creates a roof for the right upper pulmonary vein (RUPV) that stops the left-to-right shunt and redirects the vein to the left atrium. While surgical literature has clearly documented the incidence of stenosis of SVC and RUPV, sinus nodal dysfunction, and persistent residual shunts following surgical correction, it is imperative to have similar data after this new transcatheter intervention on the incidence of complications and follow-up outcomes. Since patients with pretricuspid shunts are often clinically asymptomatic, correction is primarily performed to prevent a persistent right heart volume overload and allow remodeling of the heart chambers. Any residual left-to-right shunt after a correction will result in persistent right heart dilatation. Residual flows can result from various mechanisms, including lack of apposition of the covered stent to the free edge of the SVD, fabric breach, and persistent anomalous drainage of additional right-sided pulmonary veins that drain very high in the SVC or can be due to a coexistent defect in the oval fossa. This review analyzes the different mechanisms, explains the transesophageal and angiographic images for each one, and offers solutions tailored for various reasons. Different mechanisms warrant different treatment principles. A solution for residual shunt from one mechanism may not be appropriate for residual flow through another mechanism. A thorough understanding would aid the operator in effective interventions for these SVDs., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Annals of Pediatric Cardiology.)

Transcatheter sinus venosus defect (SVD) closure with covered stents is emerging as an alternative to surgery. An adequate anchor zone in the superior vena cava is mandatory for the stability of the covered stent to prevent caudal embolization. There is a potential risk of innominate vein occlusion by the fabric of the covered stent in patients with a very short superior caval vein. Three among a total of 105 patients who underwent SVD closure at our institution developed innominate vein occlusion. Predisposing anatomical factors, identification and management of occluded innominate vein, and follow-up outcomes are discussed., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Annals of Pediatric Cardiology.)

Background: Device embolisation is a serious adverse event during transcatheter duct closure. This study analyses risk factors for embolisation., Methods: Demographic parameters, echocardiographic anatomy, haemodynamics, and procedural characteristics of consecutive duct closures in a tertiary centre over 8 years were analysed. Procedures complicated by embolisation were compared to uncomplicated procedures., Results: Fifteen embolisations occurred during 376 procedures. All except one embolisation were in infants. The pulmonary artery: aortic pressure ratio was 0.78 ± 0.22. Embolisation was seen significantly more commonly in Type C tubular ducts. Vascular plugs were more significantly associated with embolisations. Logistic regression analysis showed device embolisation was significantly higher in age group of < 6 months compared to 6-12 months (p = 0.02), higher in those with tubular ducts versus conical ducts (p = 0.003), use of vascular plugs compared to conventional duct occluders (p = 0.05), and in duct closure with undersized devices (p = 0.001). There was no in-hospital mortality. Three patients needed surgical retrieval while others were successfully managed in catheterisation laboratory., Conclusions: Device embolisation complicates 4% of transcatheter duct closures, with need for surgery in one-fifth of them. Larger ducts with high pulmonary artery pressures in younger and smaller infants are more often associated with device embolisation. Tubular ducts are more prone for embolisation compared to usual conical ducts. Softer vascular plugs are often associated with embolisations. Intentional device undersizing to avoid vascular obstruction in small patients is a frequent risk factor for embolisation. Precise echocardiographic measurements, correct occluder choice, proper technique and additional care in patients with high pulmonary artery pressures are mandatory to minimise embolisations.

Device closure has become the preferred procedure for treating oval fossa defects in the last two decades. More recently, transcatheter sinus venosus defect (SVD) closure has emerged as an alternative to surgery. Transcatheter stenting aims to overcome potential late surgical complications such as stenosis of the superior vena cava (SVC) and right upper pulmonary vein (RUPV), as well as sinus node dysfunction. Balloon interrogation of the cavoatrial junction is able to identify patients who are suitable candidates for nonsurgical closure. Successful closure is possible when the balloon seals the SVD and redirects the RUPV towards the left atrium. Oval fossa (secundum) defects can coexist in approximately 9-16% of patients with SVD. Among a group of 80 patients who underwent transcatheter closure of SVD, five adult patients aged between 22 and 52 years also required device closure of an associated oval fossa defect. The procedure involved simultaneous balloon interrogation of both the SVD and oval fossa defect, with continuous monitoring of the RUPV using bilateral femoral venous sheaths. Covered stent exclusion of the SVD was performed with concurrent device closure of the oval fossa defect using 12-36 mm atrial septal occluders. During the procedure, two patients required protective balloon inflation in the RUPV while expanding the covered stent. In one patient, a higher small accessory RUPV was intentionally left to drain into the SVC through the struts of a bare stent anchoring the covered stent in the upper SVC. In another patient, a second overlapping covered stent was used to address residual flows from a fabric tear that became apparent after balloon deflation. There were no vascular complications and only one patient exhibited an insignificant 6 mm residual flow from the caudal edge of the SVD during a follow-up of 5 to 72 months. In conclusion, the closure of both SVD and associated oval fossa defects can be successfully performed in a single procedure, with comparable procedural times and favourable mid-term outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Grow-out and hatchery units of shrimps are being impacted by disease-causing bacterial pathogens and predominantly marine Vibrios. The use of chemicals for governing bacterial pathogens in the aquaculture practices is developing resistance to bacteria. Henceforth, the application of bio-therapeutic agents from marine resources for controlling pathogens is most vital to be considered. Molecular docking is computer-assisted drug design tool to detect and counteract for drug-receptor interaction for known target protein of diseases. Therefore, an effort was made with the extract of the marine micro alga Skeletonema costatum against hemolysin protein of pathogenic bacteria Vibrio harveyi. The extract of S. costatum was tested against growth and virulence produced by V. harveyi during larviculture of Penaeus monodon. The extract was analyzed for phyto-constituents through GC-MS and used them as ligand molecule in docking. S. costatum extract at 200 µg mL -1 was found to decrease 35.20% of cumulative percentage mortality (CPM) in postlarvae of P. monodon against V. harveyi infections. The biomolecule Docasane, an alkane from the extract of S. costatum, exposed highest binding interaction than other compounds during docking analysis. The level of significance (P < 0.05) was found in CPM, growth, and virulence factors of V. harveyi studies. Thus, the present finding predicts that extract of S. costatum containing biomolecules can be recommended for use in the shrimp culture-based grow-out and hatchery units for eliminating bioluminescent V. harveyi., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The study aims to assess clinically and radiographically the success of zinc oxide eugenol, metapex, and endoflas as root canal obturating materials in primary teeth over 3, 6, and 9 months of time intervals. The randomized controlled trial was performed in 60 primary molars of 36 children aged between 4 and 9 years. Permanent restorations were given and stainless steel crowns were placed for the treated tooth. Comparing the survival proportion between the three groups was done using the Wilcoxon (Gehans) statistical test. The clinical survival variable showed 100% survival proportion for zinc oxide eugenol and endoflas, while for metapex it was 69% at the end of 9 months. The radiographical survival proportion was 100% for zinc oxide eugenol, followed by endoflas at 92% and 58% for metapex group., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Newcastle disease (ND) is highly contagious and usually causes severe illness that affects Aves all over the world, including domestic poultry. Depending on the virus's virulence, it can impact the nervous, respiratory, and digestive systems and cause up to 100% mortality. The chIFITM genes are activated in response to viral infection. The current study was conducted to quantify the mRNA of chIFITM genes in vitro in response to ND viral infection. It also examined its ability to inhibit ND virus replication in chicken embryo fibroblast (CEF) cells of the Aseel and Kadaknath breeds. Results from the study showed that the expression of all chIFITM genes was significantly upregulated throughout the period in the infected CEF cells of both breeds compared to uninfected CEF cells. In CEF cells of the Kadaknath breed, elevated levels of expression of the chIFITM 3 gene dramatically reduced ND viral growth, and the viral load was 60% lower than in CEF cells of the Aseel breed. The expression level of the chIFITMs in Kadaknath ranged from 2.39 to 11.68 log 2 folds higher than that of control CEFs and was consistently ( p < 0.01) higher than Aseel CEFs. Similar to this, the IFN-γ gene expresses strongly quickly and peaks at 13.9 log 2 fold at 48 hpi. Based on these cellular experiments, the Kadaknath breed exhibits the potential for greater disease tolerance than Aseel. However, to gain a comprehensive understanding of disease resistance mechanisms in chickens, further research involving in vivo investigations is crucial.

Emergent Coronaviridae viruses, such as SARS-CoV-1 in 2003, MERS-CoV in 2012, and SARS-CoV-2 (CoV-2) in 2019, have caused millions of deaths. These viruses have added to the existing respiratory infection burden along with respiratory syncytial virus (RSV) and influenza. There are limited therapies for respiratory viruses, with broad-spectrum treatment remaining an unmet need. Since gut fermentation of fiber produces short-chain fatty acids (SCFA) with antiviral potential, developing a fatty acid-based broad-spectrum antiviral was investigated. Molecular docking of fatty acids showed α-linolenic acid (ALA) is likely to interact with CoV-2-S, NL63-CoV-S, and RSV-F, and an ALA-containing liposome interacted with CoV-2 directly, degrading the particle. Furthermore, a combination of ALA and a SCFA-acetate synergistically inhibited CoV2-N expression and significantly reduced viral plaque formation and IL-6 and IL-1β transcript expression in Calu-3 cells, while increasing the expression of IFN-β. A similar effect was also observed in RSV-infected A549 cells. Moreover, mice infected with a murine-adapted SARS-CoV-2 (MA10) and treated with an ALA-liposome encapsulating acetate showed significant reductions in plaque-forming units present in lung tissue and in infection-associated lung inflammation and cytokines. Taken together, these results demonstrate that the ALA liposome-encapsulating acetate can be a promising broad antiviral therapy against respiratory infections.

Treatment of late-stage lung cancers remains challenging with a five-year survival rate of 8%. Immune checkpoint blockers (ICBs) revolutionized the treatment of non-small cell lung cancer (NSCLC) by reactivating anti-tumor immunity. Despite achieving durable responses, ICBs are effective in only 20% of patients due to immune resistance. Therefore, synergistic combinatorial approaches that overcome immune resistance are currently under investigation. Herein, we studied the immunomodulatory role of Withaferin A (WFA)-a herbal compound-and its effectiveness in combination with an ICB for the treatment of NSCLC. Our in vitro results show that WFA induces immunogenic cell death (ICD) in NSCLC cell lines and increases expression of the programmed death ligand-1 (PD-L1). The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process. Further, we found that a combination of WFA and α-PD-L1 significantly reduced tumor growth in an immunocompetent tumor model. Our results showed that WFA increases CD-8 T-cells and reduces immunosuppressive cells infiltrating the tumor microenvironment. Administration of NAC partially inhibited the anti-tumor response of the combination regimen. In conclusion, our results demonstrate that WFA sensitizes NSCLC to α-PD-L1 in part via activation of ROS.

Background: Generalised myasthenia gravis is a chronic, unpredictable, and debilitating rare disease, often accompanied by high treatment burden and with an unmet need for more efficacious and well tolerated treatments. Zilucoplan is a subcutaneous, self-administered macrocyclic peptide complement C5 inhibitor. We aimed to assess safety, efficacy, and tolerability of zilucoplan in patients with acetylcholine receptor autoantibody (AChR)-positive generalised myasthenia gravis., Methods: RAISE was a randomised, double-blind, placebo-controlled, phase 3 trial that was done at 75 sites in Europe, Japan, and North America. We enrolled patients (aged 18-74 years) with AChR-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America disease class II-IV), a myasthenia gravis activities of daily living (MG-ADL) score of least 6, and a quantitative myasthenia gravis score of at least 12. Participants were randomly assigned (1:1) to receive subcutaneous zilucoplan 0·3 mg/kg once daily by self-injection, or matched placebo, for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in MG-ADL score in the modified intention-to-treat population (all randomly assigned patients who received at least one dose of study drug and had at least one post-dosing MG-ADL score). Safety was mainly assessed by the incidence of treatment-emergent adverse events (TEAEs) in all patients who had received at least one dose of zilucoplan or placebo. This trial is registered at ClinicalTrials.gov, NCT04115293. An open-label extension study is ongoing (NCT04225871)., Findings: Between Sept 17, 2019, and Sept 10, 2021, 239 patients were screened for the study, of whom 174 (73%) were eligible. 86 (49%) patients were randomly assigned to zilucoplan 0·3 mg/kg and 88 (51%) were assigned to placebo. Patients assigned to zilucoplan showed a greater reduction in MG-ADL score from baseline to week 12, compared with those assigned to placebo (least squares mean change -4·39 [95% CI -5·28 to -3·50] vs -2·30 [-3·17 to -1·43]; least squares mean difference -2·09 [-3·24 to -0·95]; p=0·0004). TEAEs occurred in 66 (77%) patients in the zilucoplan group and in 62 (70%) patients in the placebo group. The most common TEAE was injection-site bruising (n=14 [16%] in the zilucoplan group and n=8 [9%] in the placebo group). Incidences of serious TEAEs and serious infections were similar in both groups. One patient died in each group; neither death (COVID-19 [zilucoplan] and cerebral haemorrhage [placebo]) was considered related to the study drug., Interpretation: Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilucoplan is a new potential treatment option for a broad population of patients with AChR-positive generalised myasthenia gravis. The long-term safety and efficacy of zilucoplan is being assessed in an ongoing open-label extension study., Funding: UCB Pharma., Competing Interests: Declaration of interests JFH has received research support (paid to his institution) from Alexion Pharmaceuticals, argenx BVBA, Cartesian Therapeutics, the US Centers for Disease Control and Prevention, the Myasthenia Gravis Foundation of America, the Muscular Dystrophy Association, the US National Institutes of Health (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), PCORI, Ra Pharmaceuticals (now UCB Biosciences), and Takeda Pharmaceuticals; honoraria from Alexion Pharmaceuticals, argenx BVBA, F Hoffman-LaRoche, Immunovant, Ra Pharmaceuticals (now UCB Biosciences), Regeneron Pharmaceuticals, Sanofi US, and Viela Bio (now Horizon Therapeutics); and non-financial support from Alexion Pharmaceuticals, argenx BVBA, Ra Pharmaceuticals (now UCB Biosciences), and Toleranzia. SB has served as a paid consultant for Sanofi Genzyme, Merck, Alexion, UCB, Biogen, and Bristol Myers Squibb. AG has served as a paid consultant for Medtronic, Atlantic Research Group, Calico, Apellis, Anexon, ALS Pharmaceuticals, QurAlis, Orion, Sanofi Genzyme, Ionis, Wave Life Therapies, Anelixis, Roche, Cytokinetics, Mitsubishi Tanabe Pharma, Amylyx, Alexion, UCB, Ra Pharmaceuticals (now UCB Biosciences), Biogen, Eli Lilly, and Amicus Therapeutics. CH has received funding for consultancy on scientific or educational advisory boards for UCB Pharma, argenx, Lupin, Roche and Biogen. HJK is a consultant for Roche, Cabaletta Bio, Lincoln Therapeutics, Takeda, and UCB Pharmaceuticals; and is chief executive officer and chief marketing office of ARC Biotechnology, based on US Patent 8,961,98. He is principal investigator of the Rare Disease Network for Myasthenia Gravis National Institute of Neurological Disorders & Stroke, and Targeted Therapy for Myasthenia Gravis. AM received funding for travel, meeting attendance, or advisory board participation from CSL Behring and UCB. RM received funding for travel, meeting attendance, or advisory board participation from Alexion, argenx, BioMarin, Catalyst, Sanofi, Regeneron, and UCB. MM has served as a paid consultant for argenx and Alexion Pharmaceuticals, and has received speaker honoraria from Asahi Kasei Medical, argenx and Alexion Pharmaceuticals. KU has served as a paid consultant for UCB Pharma, argenx, Janssen Pharma, Viela Bio, Chugai Pharma, Hanall BioPharma, and Mitsubishi Tanabe Pharma; and has received speaker honoraria from argenx, Alexion Pharmaceuticals, and the Japan Blood Products Organization. TV is the USF Site Principal Investigator for myasthenia gravis clinical trials sponsored by Alexion/AstraZeneca, argenx, Ra/UCB, Horizon/Viela Bio, Janssen/Momenta, Sanofi, Regeneron, and Cartesian Therapeutics; and has received speaking or consulting honoraria from Alexion, argenx, and UCB. MDW has received honoraria for serving on scientific advisory boards for Alexion, UCB-Ra, argenx, Biogen, Mitsubishi Tanabe Pharma, and Amylyx; consulting honoraria from Cytokinetics and CSL Behring; and speaker honoraria from Soleo Health. He also serves as a special government employee for the US Food and Drug Administration. MZ has served as a paid consultant for Signant Health. MZ was an employee of Medical University of Warsaw, Warsaw, Poland, during the conduct of the study, but is currently employed by MTZ Clinical Research powered by Pratia. BB, Melissa Brock, GdlB, PWD, and MV are employees and shareholders of UCB Pharma. RL was a Veramed consultant for UCB Pharma during the conduct of the study. Veramed are a full-service provider for UCB Pharma. RL is employed by ONO Pharma UK. MIL is funded by the UK National Health Service (Myasthenia and Related Disorders Service and National Specialised Commissioning Group for Neuromyelitis Optica, UK) and by the University of Oxford, Oxford, UK. She has been awarded research grants from the UK association for patients with myasthenia, Myaware, and the University of Oxford. She has received speaker honoraria or travel grants from Biogen Idec, Novartis, argenx, UCB, and the Guthy-Jackson Charitable Foundation. MIL serves on scientific or educational advisory boards for UCB Pharma, argenx, and Viela/Horizon. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Homochirality of the cellular proteome is attributed to the L-chiral bias of the translation apparatus. The chiral specificity of enzymes was elegantly explained using the 'four-location' model by Koshland two decades ago. In accordance with the model, it was envisaged and noted that some aminoacyl-tRNA synthetases (aaRS) that charge larger amino acids are porous to D-amino acids. However, a recent study showed that alanyl-tRNA synthetase (AlaRS) can mischarge D-alanine and that its editing domain, but not the universally present D-aminoacyl-tRNA deacylase (DTD), is responsible for correcting the chirality-based error. Here, using in vitro and in vivo data coupled with structural analysis, we show that AlaRS catalytic site is a strict D-chiral rejection system and therefore does not activate D-alanine. It obviates the need for AlaRS editing domain to be active against D-Ala-tRNAAla and we show that it is indeed the case as it only corrects L-serine and glycine mischarging. We further provide direct biochemical evidence showing activity of DTD on smaller D-aa-tRNAs that corroborates with the L-chiral rejection mode of action proposed earlier. Overall, while removing anomalies in the fundamental recognition mechanisms, the current study further substantiates how chiral fidelity is perpetuated during protein biosynthesis., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Terazosin is an α 1 -adrenergic receptor antagonist that enhances glycolysis and increases cellular ATP by binding to the enzyme phosphoglycerate kinase 1 (PGK1). Recent work has shown that terazosin is protective against motor dysfunction in rodent models of Parkinson's disease (PD) and is associated with slowed motor symptom progression in PD patients. However, PD is also characterized by profound cognitive symptoms. We tested the hypothesis that terazosin protects against cognitive symptoms associated with PD. We report two main results. First, in rodents with ventral tegmental area (VTA) dopamine depletion modeling aspects of PD-related cognitive dysfunction, we found that terazosin preserved cognitive function. Second, we found that after matching for demographics, comorbidities, and disease duration, PD patients newly started on terazosin, alfuzosin, or doxazosin had a lower hazard of being diagnosed with dementia compared to tamsulosin, an α 1 -adrenergic receptor antagonist that does not enhance glycolysis. Together, these findings suggest that in addition to slowing motor symptom progression, glycolysis-enhancing drugs protect against cognitive symptoms of PD., (© 2023. The Author(s).)

Background: Various scoring systems are available to assess the severity of cirrhosis, that is, the Child-Pugh score and Model for End-Stage Liver Disease (MELD) score. Since the liver is the major site for converting excess carbohydrates into various lipids, the deranged lipid profile can act as a prognostic biomarker of cirrhosis. We assessed the lipid profile abnormalities among patients with cirrhosis of the liver and correlated them with the severity of cirrhosisMaterials and methods: This is an analytical cross-sectional study on lipid profile as an indicator of severity in cirrhosis of the liver among patients admitted to the medical ward of a tertiary care teaching hospital in Tamil Nadu. Following detailed investigation and confirmation of cirrhosis, a fasting serum lipid profile was measured in all eligible patients with cirrhosis. Total serum cholesterol, triglyceride (TGL), and high-density lipoprotein (HDL) were measured by direct method and serum low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) were calculated by using the Friedwald formulaResults: A total of 120 patients were studied. Of them, 76 (63%) were male. Of them, alcohol (84, 75.0%), hepatitis B (8, 7.1%), and nonalcoholic steatohepatitis (NASH) (6, 5.4%) were the most common cause of cirrhosis. A clear dose-response relationship (decreasing trend) is seen in the levels of lipids for increasing severity based on the Child-Pugh score and MELD score (except for a score of ≤10). Further, the cholesterol, LDL, and HDL were significantly lower among patients with ascites or with spontaneous bacterial peritonitis compared to their respective groups. However, none of the lipid profiles significantly differed based on the presence of upper gastrointestinal (UGI) bleeding Conclusion: This study observed that there is a significant reduction in levels of lipid profile parameters like serum total cholesterol, LDL, VLDL, TGL, and HDL in patients with cirrhosis as the severity increases. Further formulation of the scoring system in association with a preexisting scoring system may provide a better assessment of patients' prognosis in view of morbidity and mortality. We recommend it is necessary to assess the fasting lipid profile in all patients with cirrhosis and prognosticate their disease progression., (© Journal of the Association of Physicians of India 2011.)

The use of dyes and segments has increased widely in recent years, but it poses a serious health risk to ecosystems. In this work, TiO 2 and two-dimensional g-C 3 N 4 nanosheets (g-CN) were fabricated through co-precipitation and thermal polymerization technique, respectively. The g-CN-TiO 2 photocatalyst (1: 3, 2: 2, 3: 1) in various weight percentages was prepared using a simple impregnation process. The photocatalytic behaviour of the g-CN, TiO 2 NPs, and different weight percentages of g-CN-TiO 2 photocatalyst was evaluated against methylene blue (MB) dye under UV-visible light illumination. Compared to pristine and other weight percentages of the g-CN-TiO 2 nanocomposite, the optimized g-CN-TiO 2 nanocomposite (3:1) showed promoted performance against MB dye. The enriched catalytic efficiency can be accredited to the low amount of TiO 2 nanoparticles deposited on gCN nanosheets, possibly due to the boosted transport properties of the electron-hole pairs. The enriched photocatalytic behaviour can be attributed to the development of the Z-scheme system between TiO 2 and g-CN. The current study is an outstanding demonstration of the development of maximum catalytic efficiency for destroying hazardous chemical dyes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Junctional ectopic tachycardia (JET) is the most common arrhythmia after pediatric open-heart surgeries (OHS), causing high morbidity and mortality. As diagnosis is often missed in patients with minimal hemodynamic instability, its incidence depends on active surveillance. A prospective randomized trial evaluated the efficacy and safety of prophylactic amiodarone and dexmedetomidine to prevent and control postoperative JET., Methods: Consecutive patients aged under 12 years were randomized into amiodarone, dexmedetomidine (initiated during anesthetic induction) and control groups. Outcome measures included incidence of JET, inotropic score, ventilation, and intensive care unit (ICU) duration and hospital stay, as well as adverse drug effects., Results: Two hundred and twenty-five consecutive patients with a median age of 9 months (range 2 days-144 months) and a median weight of 6.3 kg (range 1.8 kg-38 kg) were randomized with 70 patients each to amiodarone and dexmedetomidine groups, and the rest were controls. Ventricular septal defect and Fallot's tetralogy were the common defects. The overall incidence of JET was 16.4%. Syndromic patients, hypokalemia, hypomagnesemia, longer bypass, and cross-clamp duration were the risk factors for JET. Patients with JET had significantly prolonged ventilation ( P = 0.043), longer ICU ( P = 0.004), and hospital stay ( P = 0.034) than those without JET. JET was less frequent in amiodarone (8.5%) and dexmedetomidine (14.2%) groups compared to controls (24.7%) ( P = 0.022). Patients receiving amiodarone and dexmedetomidine had significantly lower inotropic requirements, lower ventilation duration ( P = 0.008), ICU ( P = 0.006), and hospital stay ( P = 0.05). Adverse effects such as bradycardia and hypotension after amiodarone and ventricular dysfunction after dexmedetomidine were not significantly different from controls., Conclusion: Prophylactic amiodarone or dexmedetomidine started before OHS is effective and safe for the prevention of postoperative JET., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Pediatric Cardiology.)

This study aimed to carry out the bioaugmentation of crude oil/motor oil contaminated soil. The mixture of novel strains Pseudomonas aeruginosa PP3 and Pseudomonas aeruginosa PP4 were used in this bioaugmentation studies. The four different bioaugmentation systems (BS 1-4) were carried out in this experiment labelled as BS 1 (Crude oil contaminated soil), BS 2 (BS 1 + bacterial consortia), BS 3 (Motor oil sludge contaminated soil), and BS 4 (BS 3 + bacterial consortia). The total petroleum hydrocarbon (TPH) was investigated for monitor the effectiveness of bioaugmentation process. The highest TPH removal rate was recorded on BS 4 (9091 mg Kg -1 ) was about 67% followed by 52% on BS 2 (8584 mg Kg -1 ) respectively. The percentage of biodegradation efficiency (BE) of residual crude and motor oil contaminated soil were evaluated by GCMS analysis and the results showed that 65% (BS 2) and 83% (BS 4) respectively. Further the bioaugmented soil was subjected to the plant cultivation (Lablab purpureus) and the results revealed that the L. purpureus was rapidly grown in the systems BS 4 and BS 2 than the system BS 1 and BS 2 which was due to the lesser biodegradation of the crude oil contents. In resultant, it can be concluded that the soil was suitable for the cultivation of plant. Overall, this study revealed that the selected bacterial consortia were effectively degraded the hydrocarbon and act as a potential bioremediator in the hydrocarbon polluted soil in a short period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)