Trends in the Use of Recombinant Activated Factor VII and Prothrombin Complex Concentrate in Heart Transplant Patients in Virginia.

OBJECTIVES: To explore trends in intraoperative procoagulant factor concentrate use in patients undergoing heart transplantation (HTx) in Virginia. Secondarily, to evaluate their association with postoperative thrombosis. DESIGN: Patients who underwent HTx were identified using a statewide database. Trends in off-label recombinant activated factor VII (rFVIIa) use and on-label and off-label prothrombin complex concentrate (PCC) use were tested using the Mantel-Haenszel test. Multivariate logistic regression was used to test for an association between procoagulant factor concentrate administration and thrombosis. SETTING: Virginia hospitals performing HTx. PARTICIPANTS: Adults undergoing HTx between 2012 and 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 899 patients who required HTx, 100 (11.1%) received off-label rFVIIa, 69 (7.7%) received on-label PCC, and 80 (8.9%) received off-label PCC. There was a downward trend in the use of rFVIIa over the 10-year period (p = 0.04). There was no trend in on-label PCC use (p = 0.12); however, there was an increase in off-label PCC use (p < 0.001). Patients who received rFVIIa were transfused more and had longer cardiopulmonary bypass time (p < 0.001). Receipt of rFVIIa was associated with increased thrombotic risk (odds ratio [OR] 1.92; 95% CI 1.12-3.29; p = 0.02), whereas on-label and off-label PCC use had no association with thrombosis (OR 0.98, 95% CI 0.49-1.96, p = 0.96 for on-label use; and OR 0.61, 95% CI 0.29-1.30, p = 0.20 for off-label use). CONCLUSIONS: Use of rFVIIa in HTx decreased over the past decade, whereas off-label PCC use increased. Receipt of rFVIIa was associated with thrombosis; however, patients who received rFVIIa were more severely ill, and risk adjustment may have been incomplete.

Structural DNA nanotechnology at the nexus of next-generation bio-applications: challenges and perspectives.

DNA nanotechnology has significantly progressed in the last four decades, creating nucleic acid structures widely used in various biological applications. The structural flexibility, programmability, and multiform customization of DNA-based nanostructures make them ideal for creating structures of all sizes and shapes and multivalent drug delivery systems. Since then, DNA nanotechnology has advanced significantly, and numerous DNA nanostructures have been used in biology and other scientific disciplines. Despite the progress made in DNA nanotechnology, challenges still need to be addressed before DNA nanostructures can be widely used in biological interfaces. We can open the door for upcoming uses of DNA nanoparticles by tackling these issues and looking into new avenues. The historical development of various DNA nanomaterials has been thoroughly examined in this review, along with the underlying theoretical underpinnings, a summary of their applications in various fields, and an examination of the current roadblocks and potential future directions.

Annual rhythm in immune functions of blood leucocytes in an ophidian, Natrix piscator.

Annual variations in animal's physiological functions are an essential strategy to deal with seasonal challenges which also vary according to the time of year. Information regarding annual adaptations in the immune-competence to cope with seasonal stressors in reptiles is scarce. The present research plan was designed to analyze the presence of circannual immune rhythms in defense responses of the leucocytes in an ophidian, Natrix piscator. Peripheral blood leucocytes were obtained, counted, and superoxide anion production, neutrophil phagocytosis, and nitrite release were tested to assess the innate immune functions. Peripheral blood lymphocytes were separated by centrifugation (utilizing density gradient) and the cell proliferation was measured. The Cosinor rhythmometry disclosed the presence of significant annual rhythms in the number of leucocytes, superoxide anion production, nitric oxide production, and proliferation of stimulated lymphocytes. The authors found that respiratory burst activity and proliferative responses of lymphocytes were crucial immune responses that showed the annual rhythm. It was summarized that the immune function of the N. piscator is a labile attribute that makes the animal competent to cope with the seasonal stressor by adjustment in the potency of response.

Self-assembling short peptide amphiphiles as versatile delivery agents: a new frontier in antibacterial research.

Self-assembling short peptide amphiphiles, crafted through a minimalistic approach, spontaneously generate well-ordered nanostructures, facilitating the creation of precise nanostructured biomaterials for diverse biomedical applications. The seamless integration of bioactive metal ions and nanoparticles endows them with the potential to serve as pioneering materials in combating bacterial infections. Nanomanipulation of these molecules' binary structures enables effective penetration of membranes, forming structured nanoarchitectures with antibacterial properties. Through a comprehensive exploration, we attempt to reveal the innovative potential of short peptide amphiphiles, particularly in conjugation with metal cations and nanoparticles, offering insights for future research trajectories.

Declining groundwater and its impacts along Ganga riverfronts using combined Sentinel-1, GRACE, water levels, and rainfall data.

The Indo-Gangetic Plains (IGP) in northern India are vast alluvial tracts with huge shallow aquifers, densely populated and agriculturally productive regions. In the last few decades, IGP has been facing water scarcity driven by erratic monsoon dynamics, anthropogenic activity, and hydroclimatic variability. In urban centers, continuous groundwater withdrawal leads to high stress, affecting surface deformation and a threat to buildings and infrastructures. An attempt has been made to explore the possible linkage and coupling between groundwater level, hydroclimatic variables, and subsidence in the Central Ganga Plains (CGP), in Varanasi metropolis using the combined multisensory multitemporal data, Sentinel-1 (2017-2023), GRACE (2003-2023), groundwater levels (1998-2023), and precipitation (2002-2023). Long-term hydrological response in the CGP shows continuous depletion (14.6 ± 5.6 mm/yr) in response to precipitation variability. Results show spatiotemporal variations between GWS, and precipitation estimate with nonlinear trend response due to associated inter-annual/inter-seasonal climate variability and anthropogenic water withdrawal, specifically during the observed drought years. The significant storage response in the urban center compared to a regional extent suggests the potential impact of exponentially increasing urbanization and building hydrological stress in the cities. The implications of reducing storage capacity show measured land subsidence (∼2-8 mm/yr) patterns developed along the meandering stretch of the Ganga riverfronts in Varanasi. The groundwater level data from the piezometric supports the hydroclimatic variables and subsidence coupling. Considering the vital link between water storage, food security, and socioeconomic growth, the results of this study require systematic inclusion in water management strategies as climate change seriously impacts water resources in the future.

Dynamics of land, ocean, and atmospheric parameters associated with Tauktae cyclone.

During the pre- and post-monsoon season, the eastern and western coasts are highly vulnerable to cyclones. The tropical cyclone "Tauktae" formed in the Arabian Sea on 14 May 2021 and moved along the west coast of India, and landfall occurred on 17 May 2021. During the cyclone, the maximum wind speed was 220 km/h with a pressure of 935 mb affecting meteorological, atmospheric parameters, and weather conditions of the northern and central parts of India causing devastating damage. Analysis of satellite, Argo, and ground data show pronounced changes in the oceanic, atmospheric, and meteorological parameters associated during the formation and landfall of the cyclone. During cyclone generation (before landfall), the air temperature (AT) was maximum (30.51 °C), and winds (220 km/h) were strong with negative omega values (0.3). The relative humidity (RH) and rainfall (RF) were observed to be higher at the location of the cyclone formation in the ocean and over the landfall location, with an average value of 81.28% and 21.45 mm/day, respectively. The concentration of total column ozone (TCO), CO volume mixing ratio (COVMR), H2O mass mixing ratio (H2O MMR), aerosol parameters (AOD, AE) and air quality parameter (PM) was increased over land and along the cyclone track, leading to a deterioration in the air quality. The strong wind mixes the air mass from the surroundings to the local anthropogenic emissions, and causing strong mixing of the aerosols. The detailed results show a pronounced change in the ocean, land, meteorological, and atmospheric parameters showing a strong land-ocean-atmosphere coupling associated with the cyclone.

Antimicrobial peptide mimetic minimalistic approach leads to very short peptide amphiphiles-gold nanostructures for potent antibacterial activity.

Strategically controlling concentrations of lipid-conjugated L-tryptophan (vsPA) guides the self-assembly of nanostructures, transitioning from nanorods to fibres and culminating in spherical shapes. The resulting Peptide-Au hybrids, exhibiting size-controlled 1D, 2D, and 3D nanostructures, show potential in antibacterial applications. Their high biocompatibility, favourable surface area-to-volume ratio, and plasmonic properties contribute to their effectiveness against clinically relevant bacteria. This controlled approach not only yields diverse nanostructures but also holds promise for applications in antibacterial therapeutics.

Metallopeptide nanoreservoirs for concurrent imaging and detoxification of lead (Pb) from human retinal pigment epithelial (hRPE1) cells.

Inspired by natural metallopeptides, our work focuses on engineering self-assembling nanostructures of C2-symmetric metallopeptide conjugates (MPC) from a pyridine-bis-tripeptide bioprobe that uniquely detects lead (Pb2+) ions by emitting a fluorescence signal at 450 nm, which is further intensified in the presence of DAPI (λem = 458 nm), enhancing the bioimaging quality. This study enables precise lead quantification by modulating the ionic conformation and morphology. Experimental and theoretical insights elucidate the nanostructure formation mechanism, laying the groundwork for materials encapsulation and advancing lead detoxification. Our proof-of-principle experiment, demonstrating actin filament recovery in lead-treated cells, signifies therapeutic potential for intracellular lead aggregation and introduces novel avenues in biotechnological applications within biomaterials science.

DNA tetrahedral nanocages as a promising nanocarrier for dopamine delivery in neurological disorders.

Dopamine is a neurotransmitter in the central nervous system that is essential for many bodily and mental processes, and a lack of it can cause Parkinson's disease. DNA tetrahedral (TD) nanocages are promising in bio-nanotechnology, especially as a nanocarrier. TD is highly programmable, biocompatible, and capable of cell differentiation and proliferation. It also has tissue and blood-brain barrier permeability, making it a powerful tool that could overcome potential barriers in treating neurological disorders. In this study, we used DNA TD as a carrier for dopamine to cells and zebrafish embryos. We investigated the mechanism of complexation between TD and dopamine hydrochloride using gel electrophoresis, fluorescence and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and molecular dynamic (MD) simulation tools. Further, we demonstrate that these dopamine-loaded DNA TD nanostructures enhanced cellular uptake and differentiation ability in SH-SY5Y neuroblastoma cells. Furthermore, we extended the study to zebrafish embryos as a model organism to examine survival and uptake. The research provides valuable insights into the complexation mechanism and cellular uptake of dopamine-loaded DNA tetrahedral nanostructures, paving the way for further advancements in nanomedicine for Parkinson's disease and other neurological disorders.

Ultrasonic-assisted synthesis of CaCu3Ti4O12/reduced graphene oxide composites for enhanced photocatalytic degradation of pharmaceutical products: Ibuprofen and Ciprofloxacin.

The objective of this research is to create a highly effective approach for eliminating pollutants from the environment through the process of photocatalytic degradation. The study centers around the production of composites consisting of CaCu3Ti4O12 (CCTO) and reduced graphene oxide (rGO) using an ultrasonic-assisted method, with a focus on their capacity to degrade ibuprofen (IBF) and ciprofloxacin (CIP) via photodegradation. The impact of rGO on the structure, morphology, and optical properties of CCTO was inspected using XRD, FTIR, Raman, FESEM, XPS, BET, and UV-Vis. Morphology characterization showed that rGO particles were dispersed within the CCTO matrix without any specific chemical interaction between CCTO and C in the rGO. The BET analysis revealed that with increasing the amount of rGO in the composite, the specific surface area significantly increased compared to the CCTO standalone. Besides, increasing rGO resulted in a reduction in the optical bandgap energy to around 2.09 eV, makes it highly promising photocatalyst for environmental applications. The photodegradation of IBF and CIP was monitored using visible light irradiation. The results revealed that both components were degraded above 97% after 60 min. The photocatalyst showed an excellent reusability performance with a slight decrease after five runs to 93% photodegradation efficiency.

CA19-9 and CEA biosensors in pancreatic cancer.

Cancer is a complex pathophysiological condition causing millions of deaths each year. Early diagnosis is essential especially for pancreatic cancer. Existing diagnostic tools rely on circulating biomarkers such as Carbohydrate Antigen 19-9 (CA19-9) and Carcinoembryonic Antigen (CEA). Unfortunately, these markers are nonspecific and may be increased in a variety of disorders. Accordingly, diagnosis of pancreatic cancer generally involves more invasive approaches such as biopsy as well as imaging studies. Recent advances in biosensor technology have allowed the development of precise diagnostic tools having enhanced analytical sensitivity and specificity. Herein we examine these advances in the detection of cancer in general and in pancreatic cancer specifically. Furthermore, we highlight novel technologies in the measurement of CA19-9 and CEA and explore their future application in the early detection of pancreatic cancer.

System of wheat intensification (SWI): Effects on lodging resistance, photosynthetic efficiency, soil biomes, and water productivity.

Intense cultivation with narrow row spacing in wheat, a common practice in the Indo-Gangetic plains of South Asia, renders the crop more susceptible to lodging during physiological maturity. This susceptibility, compounded by the use of traditional crop cultivars, has led to a substantial decline in overall crop productivity. In response to these challenges, a two-year field study on the system of wheat intensification (SWI) was conducted. The study involved three different cultivation methods in horizontal plots and four wheat genotypes in vertical plots, organized in a strip plot design. Our results exhibited that adoption of SWI at 20 cm × 20 cm resulted in significantly higher intercellular CO2 concentration (5.9-6.3%), transpiration rate (13.2-15.8%), stomatal conductance (55-59%), net photosynthetic rate (126-160%), and photosynthetically active radiation (PAR) interception (1.6-25.2%) over the existing conventional method (plant geometry 22.5 cm × continuous plant to plant spacing) of wheat cultivation. The lodging resistance capacity of both the lower and upper 3rd nodes was significantly higher in the SWI compared to other cultivation methods. Among different genotypes, HD 2967 demonstrated the highest recorded value for lodging resistance capacity, followed by HD 2851, HD 3086, and HD 2894. In addition, adoption of the SWI at 20 cm × 20 cm enhanced crop grain yield by 36.9-41.6%, and biological yield by 27.5-29.8%. Significantly higher soil dehydrogenase activity (12.06 µg TPF g-1 soil hr-1), arylsulfatase activity (82.8 µg p-nitro phenol g-1 soil hr-1), alkaline phosphatase activity (3.11 n moles ethylene g-1 soil hr-1), total polysaccharides, soil microbial biomass carbon, and soil chlorophyll content were also noted under SWI over conventional method of the production. Further, increased root volumes, surface root density and higher NPK uptake were recorded under SWI at 20×20 cm in comparison to rest of the treatments. Among the tested wheat genotypes, HD-2967 and HD-3086 had demonstrated notable increases in grain and biological yields, as well as improvements in the photosynthetically active radiation (PAR) and chlorophyll content. Therefore, adoption of SWI at 20 cm ×20 cm (square planting) with cultivars HD 2967 might be the best strategy for enhancing crop productivity and resource-use efficiency under the similar wheat growing conditions of India and similar agro-ecotypes of the globe.

Cardiac Reverse Remodeling Mediated by HeartMate 3 Left Ventricular Assist Device: Comparison to Older Generation Devices.

Currently, the fully magnetically levitated left ventricular assist device (LVAD) HeartMate 3 (HM3) is the only commercially available device for advanced heart failure (HF) patients. However, the left ventricular (LV) functional and structural changes following mechanical unloading and circulatory support (MCS) with the HM3 have not been investigated. We compared the reverse remodeling induced by the HM3 to older generation continuous-flow LVADs. Chronic HF patients (n = 405) undergoing MCS with HeartWare Ventricular Assist Device (HVAD, n = 115), HM3 (n = 186), and HeartMate II (HM2, n = 104) at four programs were included. Echocardiograms were obtained preimplant and at 1, 3, 6, and 12 months following LVAD implantation. There were no differences in the postimplant serial LV ejection fraction (LVEF) between the devices. The postimplant LV internal diastolic diameter (LVIDd) was significantly lower for HM2 at 3 and 6 months compared with HVAD and HM3. The proportion of patients achieving "cardiac reverse remodeling responder" status (defined as LVEF improvement to ≥40% and LVIDD ≤5.9 cm) was 11.9%, and was similar between devices. HeartMate 3 appears to result in similar cardiac reverse remodeling as older generation CF-LVADs, suggesting that the fully magnetically levitated device technology could provide an effective platform to further study and promote cardiac reverse remodeling.

Dynamic Risk Estimation of Adverse Events in Ambulatory LVAD Patients: A MOMENTUM 3 Analysis.

BACKGROUND: Hemocompatibility-related adverse events affect patients after left ventricular assist device (LVAD) implantation but are hard to predict. OBJECTIVES: Dynamic risk modeling with a multistate model can predict risk of gastrointestinal bleeding (GIB), stroke, or death in ambulatory patients. METHODS: This was a secondary analysis of the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial. HeartMate 3 LVAD recipients who survived to hospital discharge and were followed for up to 2 years. A total of 145 variables were included in the multistate model with multivariate logistic regression. Model performance was assessed with the area under the curve in a holdout validation cohort. A risk stratification tool was created by dividing patients into categories of predicted risk using the final model variables and associated OR. RESULTS: Among 2,056 LVAD patients, the median age was 59.4 years (20.4% women, 28.6% Black). At 2 years, the incidence of GIB, stroke, and death was 25.6%, 6.0%, and 12.3%, respectively. The multistate model included 39 total variables to predict risk of GIB (16 variables), stroke (10 variables), and death (19 variables). When ambulatory patients were classified according to their risk category, the 30-day observed event rate in the highest risk group for GIB, stroke, or death was 26.9%, 1.8%, and 4.8%, respectively. The multistate model predicted GIB, stroke, and death at any 30-day period with an area under the curve of 0.70, 0.69, and 0.86, respectively. CONCLUSIONS: The multistate model informs 30-day risk in ambulatory LVAD recipients and allows recalculation of risk as new patient-specific data become available. The model allows for accurate risk stratification that predicts impending adverse events and may guide clinical decision making. (MOMENTUM 3 IDE Clinical Study Protocol; NCT02224755).

Sex-Related Differences in Patient Characteristics, Hemodynamics, and Outcomes of Cardiogenic Shock: INOVA-SHOCK Registry.

Background: Little is known about sex-related differences in outcomes of patients with cardiogenic shock (CS) treated within a standardized team-based approach (STBA). Methods: We evaluated 520 consecutive patients (151 women and 369 men) with CS due to acute myocardial infarction (AMI) and heart failure (HF) in a single-center registry (January 2017-December 2019) and examined outcomes according to sex and CS phenotype. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiac events, 30-day mortality, major bleeding, vascular complications, and stroke. Results: Women with AMI-CS had higher baseline acuity (CardShock score: female [F]: 5.5 vs male [M]: 4.0; P = .04). Women with HF-CS more often presented with cardiac arrest (F: 12.4% vs M: 2.4%; P< .01) and had higher rates of vasopressor use (F: 70.8% vs M: 58.0%; P = .04) and mechanical circulatory support (F: 46.1% vs M: 32.5%; P = .04). There were no sex-related differences in in-hospital mortality for AMI-CS (F: 45.2% vs M: 36.9%; P = .28) and HF-CS (F: 28.1% vs M: 24.5%; P = .56). Women with HF-CS experienced higher rates of major bleeding (F: 25.8% vs M: 13.7%; P = .02) and vascular complications (F: 15.7% vs M: 6.1%; P = .01). However, female sex was not an independent predictor of these complications. No sex differences in survival were noted at 1 year. Conclusions: Within an STBA, although women with AMI-CS and HF-CS presented with higher acuity, they experienced similar in-hospital mortality, major adverse cardiac events, 30-day mortality, stroke, and 30-day readmissions as men. Further research is needed to better understand the extent to which historical differences in CS outcomes can be mitigated by an STBA.

3D Rapid Prototyping Heart Model Validation for Teaching and Training - A Pilot Project in a Teaching Institution

Abstract Introduction: Rapid prototyping is a process by which three-dimensional (3D) computerized surface models are converted into physical models. In this study, a 3D heart bio model was created using the rapid prototyping method and the accuracy of this heart model was assessed by clinicians. Methods: The two-dimensional images of normal heart from gated computed tomography scan datasets were used to create a 3D model of the heart. The slices were then processed using the software BioModroid and printed with the 3D printer. The evaluation of the model was performed by a questionnaire answered by four cardiothoracic surgeons, 12 cardiologists, five radiologists, and nine surgical registrars. Results: Eighty-six percent of the anatomy structures showed in this model scored 100% accuracy. Structures such as circumflex branch of left coronary artery, great cardiac vein, papillary muscle, and coronary sinus were each rated 77%, 70%, 70%, and 57% accurate. Among 30 clinicians, a total of 93% rated the model accuracy as good and above; 64% of the clinicians evaluated this model as an excellent teaching tool for anatomy class. As a visual aid for surgery or interventional procedures, the model was rated excellent (40%), good (50%), average (23%), and poor (3%); 70% of the clinicians scored the model as above average for training purpose. Overall, this 3D rapid prototyping cardiac model was rated as excellent (33%), good (50%), and average (17%). Conclusion: This 3D rapid prototyping heart model will be a valuable source of anatomical education and cardiac interventional management.

Syndrome of ventricular septal defect and aortic regurgitation - A 22-year review of its management

Abstract Introduction: The presence of aortic regurgitation (AR) in the setting of ventricular septal defect (VSD) has always been a management challenge. Methods: This is a retrospective study looking at patients who underwent VSD closure with or without aortic valve intervention between January 1st, 1992 and December 31st, 2014 at the Institute Jantung Negara. This study looked at all cases of VSD and AR, where AR was classified as mild, moderate, and severe, the intervention done in each of this grade, and the durability of that intervention. The interventions were classified as no intervention (NI), aortic valve repair (AVr), and aortic valve replacement (AVR). Results: A total of 261 patients were recruited into this study. Based on the various grades of AR, 105 patients had intervention to their aortic valve during VSD closure. The rest 156 had NI. All patients were followed up for a mean time of 13.9±3.5 years. Overall freedom from reoperation at 15 years was 82.6% for AVr. Various factors were investigated to decide on intervening on the aortic valve during VSD closure. Among those that were statistically significant were the grade of AR, size of VSD, age at intervention, and number of cusp prolapse. Conclusion: We can conclude from our study that all moderate and severe AR with small VSD in older patients with more than one cusp prolapse will need intervention to their aortic valve during the closure of VSD.