Co-stabilization effects of gluten/carrageenan to the over-heated myofibrillar protein: Inhibit the undesirable gel weakening and protein over-aggregations.

High-temperature (120 °C) sterilization is an indispensable process for manufacturing ready-to-eat surimi products, yet risking the denaturation of their myofibrillar proteins (MP), thus significantly reducing the gelling properties. To resolve this problem, herein, a synergistic co-strengthening strategy was designed. The negatively charged polysaccharide carrageenan (CG) was introduced into MP simultaneously with wheat gluten, followed by 120 °C thermal treatment for 30 min. A substantial enhancement in mechanical strength, up to four times greater (from 9.86 to 42.38 g·cm), was observed for MP gels, which even surpassed that subjected to conventional gelation processes at 90 °C (36.53 g·cm). Gels that were concurrently added with gluten and CG exhibited porous networks, uniform water distribution, and improved water holding capacity. Accordingly, over-aggregation behaviors of MP were restricted, as evidenced by their reduced particle sizes and polymer dispersity index. Other heat-induced protein deteriorations at 120 °C, i.e., changes of secondary structures and disulfide bonding conformations, were also alleviated. By varying the CG types, it was shown that the κ-CG/gluten-added MP achieved highest gel strength, while the ι-CG/gluten combination may better stabilize the moisture in gel networks. This study introduces a co-reinforcement paradigm and scientific insights to the quality improvement of ready-to-eat meat products.

Changes of structure properties and potential allergenicity of ovalbumin under high hydrostatic pressures.

Egg proteins, notably ovalbumin (OVA), contribute to a prevalent form of food allergy, particularly in children. This study aims to investigate the impact of high hydrostatic pressure (HHP) treatment at varying levels (300, 400, 500, and 600 MPa) on the molecular structure and allergenicity of OVA. The structure of HHP-treated OVA was assessed through fluorescence spectroscopy, circular dichroism spectroscopy, and molecular dynamics (MD) simulation. HHP treatment (600 MPa) altered OVA structures, such as α-helix content decreased from 28.07 % to 19.47 %, and exogenous fluorescence intensity increased by 8.8 times compared to that of the native OVA. The free sulfhydryl groups and zeta potential value were also increased with HHP treatment (600 MPa). ELISA analysis and MD simulation unveiled a noteworthy reduction in the allergenicity of OVA when subjected to 600 MPa for 10 min. Overall, this study suggests that the conformational changes in HHP-treated OVA contribute to its altered allergenicity.

Molecular Property Diagnostic Suite for COVID-19 (MPDSCOVID-19): an open-source disease-specific drug discovery portal.

Molecular Property Diagnostic Suite (MPDS) was conceived and developed as an open-source disease-specific web portal based on Galaxy. MPDSCOVID-19 was developed for COVID-19 as a one-stop solution for drug discovery research. Galaxy platforms enable the creation of customized workflows connecting various modules in the web server. The architecture of MPDSCOVID-19 effectively employs Galaxy v22.04 features, which are ported on CentOS 7.8 and Python 3.7. MPDSCOVID-19 provides significant updates and the addition of several new tools updated after six years. Tools developed by our group in Perl/Python and open-source tools are collated and integrated into MPDSCOVID-19 using XML scripts. Our MPDS suite aims to facilitate transparent and open innovation. This approach significantly helps bring inclusiveness in the community while promoting free access and participation in software development. Availability & Implementation: The MPDSCOVID-19 portal can be accessed at https://mpds.neist.res.in:8085/.

Analyzing the cation-aromatic interactions in proteins: Cation-aromatic database V2.0.

The cation-aromatic database (CAD) is a comprehensive repository of cation-aromatic motifs found in experimentally determined protein structures, first reported in 2007 [Proteins, 2007, 67, 1179]. The present article is an update of CAD that contains information of approximately 27.26 million cation-aromatic motifs. CAD uses three distance parameters (r, d1, and d2) to determine the position of the cation relative to the centroid of the aromatic residue and classifies the motifs as cation-π or cation-σ interactions. As of June 2023, about 193 936 protein structures were retrieved from Protein Data Bank, and this resulted in the identification of an impressive number of 27 255 817 cation-aromatic motifs. Among these motifs, spherical motifs constituted 94.09%, while cylindrical motifs made up the remaining 5.91%. When considering the interaction of metal ions with aromatic residues, 965 564 motifs are identified. Remarkably, 82.08% of these motifs involved the binding of metal ions to the amino acid HIS. Moreover, the analysis of binding preferences between cations and aromatic residues revealed that the HIS-HIS, PHE-ARG, and TRP-ARG pairs exhibited a preferential geometry. The motif pair HIS-HIS was the most prevalent, accounting for 19.87% of the total, closely followed by TYR-LYS at 10.17%. Conversely, the motif pair TRP-HIS had the lowest occurrence, representing only 4.20% of the total. The data generated help in revealing the characteristics and biological functions of cation-aromatic interactions in biological molecules. The updated version of CAD (Cation-Aromatic Database V2.0) can be accessed at https://acds.neist.res.in/cadv2.

E-IMNCI: a novel clinical diagnostic support system approach to strengthen effectiveness and quality of IMNCI implementation in India.

Integrated management of childhood illness is a globally proven primary care strategy to improve child survival and is being implemented worldwide in countries with high burden of child mortality. Its implementation as Integrated Management of Newborn and Childhood Illness (IMNCI) in India has been challenging.The primary objective of the present work was to assess the feasibility, acceptability and use of an adapted Integrated E Diagnostic Approach (IeDA) that provides e-Learning and improved clinical practices of the primary level health service provider auxiliary nurse midwives (ANMs) to deliver IMNCI services. This India-specific approach was contextualised to the Indian IMNCI programme based on 7 years of IeDA implementation learning from West Africa.The Integrated Management of Neonatal and Childhood Illness pilot was implemented across 80 front-line workers, 70 ANMs and 10 medical officers) in 55 facilities of 3 blocks of Ranchi district, Jharkhand. This report evaluated the feasibility of its use by ANMs only. Based on the results, it can be concluded that it is possible to implement the newly developed application. A total of 2500 cases were managed by ANMs using the application till May 2020. All ANMs used it to provide treatment to the children. 63% of ANMs used it to provide medications, 83% for counselling and 71% for follow-up as per the recommendations. The app is highly acceptable to ANMs for use as a clinical case management tool for childhood illness. There were some improvements in case management in both the age group (0-59 days and 2-12 months) of children. 78% of caregivers responded with their desire to revisit the health facility in future, highlighting the contribution of an e-tool in improving the perception of the caregiver.

Molecular Property Diagnostic Suite Compound Library (MPDS-CL): a structure-based classification of the chemical space.

Molecular Property Diagnostic Suite Compound Library (MPDS-CL) is an open-source Galaxy-based cheminformatics web portal which presents a structure-based classification of the molecules. A structure-based classification of nearly 150 million unique compounds, obtained from 42 publicly available databases and curated for redundancy removal through 97 hierarchically well-defined atom composition-based portions, has been done. These are further subjected to 56-bit fingerprint-based classification algorithm which led to the formation of 56 structurally well-defined classes. The classes thus obtained were further divided into clusters based on their molecular weight. Thus, the entire set of molecules was put into 56 different classes and 625 clusters. This led to the assignment of a unique ID, named as MPDS-AadharID, for each of these 149,169,443 molecules. MPDS-AadharID is akin to the unique number given to citizens in India (similar to SSN in the US and NINO in the UK). The unique features of MPDS-CL are (a) several search options, such as exact structure search, substructure search, property-based search, fingerprint-based search, using SMILES, InChIKey and key-in; (b) automatic generation of information for the processing for MPDS and other galaxy tools; (c) providing the class and cluster of a molecule which makes it easier and fast to search for similar molecules and (d) information related to the presence of the molecules in multiple databases. The MPDS-CL can be accessed at https://mpds.neist.res.in:8086/ .

Analyzing the aromatic-aromatic interactions in proteins: A2ID 2.0.

The Aromatic-Aromatic Interactions Database (A2ID) is a comprehensive repository dedicated to documenting aromatic-aromatic (π-π) networks observed in experimentally determined protein structures. The first version of A2ID was reported in 2011 [Int J Biol Macromol, 2011, 48, 540]. It has undergone a series of significant updates, leading to its current version, which focuses on the identification and analysis of 3,444,619 π-π networks from proteins. The geometrical parameters such as centroid-centroid distances (r) and interplanar angles (ϕ) were used to identify and characterize π-π networks. It was observed that among the 84,500 proteins with at least one aromatic π-π network, about 92.50 % of the instances are found to be either 2π (77.34 %) or 3π (15.23 %) networks. The analysis of interacting amino acid pairs in 2π networks indicated a dominance of PHE residues followed by TYR. The updated version of A2ID incorporates analysis of π-π networks based on SCOP2 and ECOD classifiers, in addition to the existing SCOP, CATH, and EC classifications. This expanded scope allows researchers to explore the characteristics and functional implications of π-π networks in protein structures from multiple perspectives. The current version of A2ID along with its extensive dataset and detailed geometric information is publicly accessible using https://acds.neist.res.in/a2idv2.

Tracing the transition from covalent to non-covalent functionalization of pyrene through C-, N-, and O-based ionic and radical substrates using quantum mechanical calculations.

Pyrene is one of the widely investigated aromatic hydrocarbons given its unique optical and electronic properties. Modulating inherent characteristics of pyrene via covalent or non-covalent functionalization has been attractive for a wide variety of advanced biomedical and other device applications. In this study, we have reported the functionalization of pyrene via C, N, and O based ionic and radical substrates, and emphasized the transition of covalent to non-covalent functionalization through making the modulation in the substrate. As expected, strong interactions were observed for cationic substrates, however, anionic substrates also exhibited a competitive binding strength. For instance, methyl and phenyl substituted CH3 complexes exhibited IEs in the range of -17 kcal mol-1 to -127 kcal mol-1 and -14 kcal mol-1 to -95 kcal mol-1 and for cationic and anionic substrates, respectively. The analysis of topological parameters showed that un-substituted cationic, anionic, and radical substrates interact with pyrene via covalent interactions, and further become non-covalent upon methylation and phenylation of the substrates. In cationic complexes, the polarisation component is observed to be dominating the interactions, whereas highly competitive contributions from polarization and exchange components were observed in anionic and radical complexes. The contribution of the dispersion component increases with an increase in the degree of methylation and phenylation of the substrate, and starts dominating once the interactions become non-covalent in nature.

First example of ambipolar naphthalene diimide exhibiting a room temperature columnar phase.

A self-assembled ambipolar organic semiconductor based on naphthalene diimide with low clearing temperature, solution processability, and high molar extinction coefficient, exhibiting a room temperature columnar hexagonal liquid crystalline phase is reported.

Binding propensity and selectivity of cationic, anionic, and neutral guests with model hydrophobic hosts: A first principles study.

Computations play a critical role in deciphering the nature of host-guest interactions both at qualitative and quantitative levels. Reliable quantum chemical computations were employed to assess the nature, binding strength, and selectivity of ionic, and neutral guests with benzenoid hosts. Optimized complex structures reveal that alkali and ammonium ions are found to be in the hydrophobic cavity, while halide ions are outside, while both complexes elicit substantial binding energy. The origin of the selectivity of host toward the guest has been traced to the interaction and deformation energies, and the nature of associated interactions is quantified using energy decomposition and the Quantum Theory of Atoms in Molecules analyses. While the larger hosts lead to loosely bound complexes, as assessed by the longer intermolecular distances, the binding strengths are proportional to the size of the host systems. The binding of cationic complexes is electrostatic or polarization driven while exchange term dominates the anionic complexes. In contrast, dispersion contribution is a key in neutral complexes and plays a pivotal role in stabilizing the polyatomic complexes.

Towards systematic exploration of chemical space: building the fragment library module in molecular property diagnostic suite.

A fragment-based drug discovery (FBDD) approach has traditionally been of utmost significance in drug design studies. It allows the exploration of large chemical space to find novel scaffolds and chemotypes which can be improved into selective inhibitors with good affinity. In the current work, several public domain chemical libraries (ChEMBL, DrugCentral, PDB ligands, COCONUT, and SAVI) comprising bioactive and virtual molecules were retrieved to develop a fragment library. A systematic fragmentation method that breaks a given molecule into rings, linkers, and substituents was used to cleave the molecules and the fragments were analyzed. Further, only the ring framework was taken into the consideration to develop a fragment library that consists of a total number of 107,614 unique fragments. This set represents a rich diverse structure framework that covers a wide variety of yet-to-be-explored fragments for a wide range of small molecule-based applications. This fragment library is an integral part of the molecular property diagnostic suite (MPDS) suite that can be used with other modeling and informatics methods for FBDD approaches. The fragment library module of MPDS can be accessed at http://mpds.neist.res.in:8085 .

Numerical Analysis of Temperature Distribution Profiles of Breast Tissues with Cyst and Tumor of Different sizes and Locations.

Breast cancer causes more deaths among all types of cancers. Efforts have been put to study the change in temperature distribution profile of the breast in presence of an abnormality. By applying Pennes's bio-heat equation, a 2D finite element model is developed for the heat transfer mechanism. Surface temperature gradients due to the presence of abnormalities at various depths and sizes are analyzed. The results show that the presence of a cyst decreases the temperature whereas the occurrence of tumor increases the temperature inside the breast. It is observed that abnormal tissue having a radius less than 1.5cm and depth greater than 5cm, has a negligible effect on the surface temperature profile. The highest change in surface temperature is observed when a cyst or tumor is larger and present near the skin. The simulation results help in the better interpretation of the thermal images and calibration of infrared camera. This study could be helpful in the early diagnosis of breast cancer.

6-Ethoxy-4- N-(2-morpholin-4-ylethyl) -2-N-propan-2-yl-1,3, 5-triazine-2, 4-diamine endows herbicidal activity against Phalaris minor a weed of wheat crop field: An in -silico and experimental approaches of herbicide discovery.

Phalaris minor is a major weed of wheat crop which has evolved resistance against herbicides. Isoproturon is the most accepted herbicide developed resistance in 1992. Later, introduced herbicides also developed resistance and cross-resistance to their respective binding sites. Isoproturon binds at the QB binding site of the D1 protein of photosystem-II (PS-II), which blocks the electron transfer in photosynthesis. In this work, we have carried out a series of computational studies to prioritize the promising herbicides against D1 protein of P. minor. Through the computational studies, twenty-four lead molecules are prioritized which have shown a higher binding affinity and inhibition constant than the reference ligand molecule. The binding and conformational stability of docked complexes was evaluated by molecular dynamics simulations and binding free energy calculations i.e., MM/PBSA. A list of amino acids such as Ala225, Ser226, Phe227, and Asn229 present in the binding site of protein is obtained to be playing an important role in the stability of the protein-lead complex via hydrogen bond and π-π interactions. Binding free energy calculation revealed that the selected lead molecule binding is energetically favorable and driven by electrostatic interactions. Among 24 leads, computational results have uncovered eight promising compounds as potential herbicides which have shown comparable physiochemical profile, better docking scores, system stability, H-bond occupancy, and binding free energy than terbutryn, a reference molecule. These prioritized molecules were custom synthesized and evaluated for their herbicidal activity and specificity through whole plant assay under laboratory-controlled conditions. The lead molecule ELC5 (6-ethoxy-4-N-(2-morpholin-4-ylethyl)-2-N-propan-2-yl-1,3,5-triazine-2,4-diamine) has shown comparable activity to the reference herbicide(isoproturon) against P. minor.

Repurposing of approved drug molecules for viral infectious diseases: a molecular modelling approach.

The identification of new viral drugs has become a task of paramount significance due to the frequent occurrence of viral infections and especially during the current pandemic. Despite the recent advancements, the development of antiviral drugs has not made parallel progress. Reduction of time frame and cost of the drug development process is the major advantage of drug repurposing. Therefore, in this study, a drug repurposing strategy using molecular modelling techniques, i.e. biological activity prediction, virtual screening, and molecular dynamics simulation was employed to find promising repurposing candidates for viral infectious diseases. The biological activities of non-redundant (4171) drug molecules were predicted using PASS analysis, and 1401 drug molecules were selected which showed antiviral activities in the analysis. These drug molecules were subjected to virtual screening against the selected non-structural viral proteins. A series of filters, i.e. top 10 drug molecules based on binding affinity, mean value of binding affinity, visual inspection of protein-drug complexes, and number of H-bond between protein and drug molecules were used to narrow down the drug molecules. Molecular dynamics simulation analysis was carried out to validate the intrinsic atomic interactions and binding conformations of protein-drug complexes. The binding free energies of drug molecules were assessed by employing MMPBSA analysis. Finally, nine drug molecules were prioritized, as promising repurposing candidates with the potential to inhibit the selected non-structural viral proteins.Communicated by Ramaswamy H. Sarma.

Fate of Sc-Ion Interaction With Water: A Computational Study to Address Splitting Water Versus Solvating Sc Ion.

An exhaustive study of Sc-ion interaction with water molecules in all its possible oxidation and spin states has been carried out to delineate the relative propensity of Sc ions toward solvation and water splitting. Potential energy surface analysis of the Sc-ion reaction with water molecules, topological analysis of bonds, and the effect of sequential solvation up to 6 water molecules have been examined. Calculated values showed good agreement with the available experimental results. Close-shell systems such as singlet mono- and tricationic Sc ions prefer to split the water molecules. In contrast, the open-shell systems such as triplet mono- and doublet dicationic Sc ions prefer to get solvated than split the water molecule. Topological analysis of electron density predicted the Sc+/2+-water bond as a noncovalent bond while Sc3+-OH2, Sc2+-OH, and Sc+-H bonds as partially covalent in nature. Energy decomposition analysis revealed that Sc ion-water interactions are driven by electrostatic energy followed by polarization energy. The current study reveals that transition metal catalysis can be one of the most effective tools to employ in water splitting, by properly tuning the electrons, spin, and ligands around the catalytic center.

Study of lipid heterogeneity on bilayer membranes using molecular dynamics simulations.

Human cell membranes consist of various lipids that are essential for their structure and function. It typically comprises phosphatidylcholine (POPC), phosphatidylethanolamine (POPE), phosphatidylserine (POPS), sphingomyelin (PSM), and cholesterol (CHL). Several experimental and computational techniques have been employed to characterize the composition of human cell membranes, however, CHL enriched membrane is still not clearly understood through these techniques. Molecular dynamics simulation results illustrated the biophysical properties of heterogeneous membranes based on the lipid composition as well as the concentration of lipids, exclusively for CHL and PSM. Herein, we have investigated the structure-function relationships of lipids comparatively to delineate the effect of heterogeneity on the biophysical properties of different membranes. It has been observed that the significant fraction of CHL (i.e., ~33% in ternary, ~25% in quaternary, and ~16% in senary type bilayers) in combination with other lipids introduced compactness, and increased the thickness of the membrane. The analysis of lipid mass density stated that the density of lipid head group, phosphate, and glycerol-ester in presence of CHL with or without PSM is an underlying reason for membrane ordering. Results also revealed that the presence of POPI and POPS are the reasons for an adequate drop in the ordering of lipid chain, particularly on POPE chain. The self-interaction of CHL, PSM, POPE and the interaction of CHL and POPC with POPE seem to determine the structure and function of the heterogeneous membrane. Our findings provide a qualitative understanding of the effect of membrane heterogeneity on the physiological properties of membranes. The structures inspected in this study would help to select the heterogeneous bilayer model to mimic the human cell membranes to analyse or characterize the membrane-associated phenomena.

Towards developing a criterion to characterize non-covalent bonds: a quantum mechanical study.

Chemical bonds are central to chemistry, biology, and allied fields, but still, the criterion to characterize an interaction as a non-covalent bond has not been studied rigorously. Therefore, in this study, we have attempted to characterize the non-covalent bonds by considering a total of 85 model systems depicting different chemical bonds comprising 43 non-covalent and 42 other bonds such as covalent, ionic, and coordinate bonds. The characterization has been done based on interaction energy, energy decomposition analysis (EDA), the NCI plot, and the analysis of topological properties of electron density. The interaction energy values, energy decomposition analysis, and NCI plot give insights into the full understanding of bond strength and its nature, but they fail to distinctively characterize the interaction as a non-covalent bond. Herein, a special criterion has been developed based on the topological parameters to characterize an interaction as a non-covalent bond. Topological parameters illustrate that the values of both ∇2ρ and H(r) are positive with a value of ρ < 0.03 a.u. and [-G(r)/V(r)] ≥ 1.00 for the non-covalent bonds. The value of ρ increases up to 0.06 a.u. with a positive value of ∇2ρ and a negative value of H(r) if the non-covalent bond is partially covalent in nature. The analysis of G(r) suggests that it dominates the H(r) of non-covalent bonds with greater than 50% contribution, whereas the contribution of G(r) varies between 35 and 50% in the case of bonds which are partially covalent in nature. The criterion based on topological parameters is likely to be very helpful to comprehend and ascertain the non-covalent bonds in the chemical as well as complex biological systems.

The prevalence of developmental anomalies among school children in Southern district of Andhra Pradesh, India.

BACKGROUND: The developmental anomalies of oral cavity are malformations affecting dental and oral tissues. Anomalies of teeth can be associated with primary, mixed or adult dentitions. Anomalies are the results of perturbations in the developmental stages of tissues which may be influenced by genetic and/or environmental factors. AIM AND OBJECTIVES: The primary objective of this study was to estimate the prevalence of oral and dental anomalies among school attending children in Chittoor and Kadapa districts of Andhra Pradesh. The secondary objective of this study was to compare occurrence of anomalies based on the age stratification to denote primary, mixed and adult dentitions. MATERIALS AND METHODS: A total of 5000 school children, aged 3-15 years were invited to participate in the study. Information regarding age, sex, level of school education, brushing and hygiene habits were collected using a questionnaire. Intra- and extra-oral examinations were conducted by trained dental surgeons. Clinical data were collected by a single examiner and the details of these anomalies were recorded on the data sheet of the study. The obtained data were statistically analyzed using Chi-square test. RESULTS: Overall prevalence of developmental anomalies was 11.40% and documented 14 types of anomalies. The prevalence of documented anomalies is as follows: tongue-tie 197 (3.90%), dental fluorosis 171 (3.40%), high frenal attachments 156 (3.10%), cusp of Carabelli 14 (0.30%), supernumerary teeth 11 (0.20%), microdontia 4 (0.10%), congenitally missing teeth 4 (0.10%), lip pits 3 (0.08%), fusion 2 (0.04%), retained deciduous teeth 2 (0.04%) and one case of angular cheilitis, cleft lip and cleft palate, talon cusp, amelogenesis imperfecta (0.02%). The prevalence of dental anomalies was 18.10% in 3-5 years, 52.30% among 6-12 years and 29.6% in 13-15 years. Chi-square test was statistically significant (P = 0.003). CONCLUSIONS: Tongue-tie was the most frequent oral tissue developmental anomaly and fluorosis was the most common developmental anomaly affecting dental tissue. The prevalence rate of the study was compared with studies published from other geographical regions in India. The variations in the reported prevalence of developmental anomalies are probably related to genetic and environmental conditions.

Timing of vancomycin prophylaxis for cardiac surgery patients and the risk of surgical site infections.

BACKGROUND: Increased incidence of methicillin-resistant Staphylococcus species has required some hospitals to choose vancomycin for surgical prophylaxis. Guidelines for appropriate timing of vancomycin prophylaxis state that the infusion should begin within 120 min before the first surgical incision. However, no studies have investigated the proper timing of vancomycin prophylaxis in relationship to surgical site infections (SSI). The objective of the present study was to assess the effect of vancomycin prophylaxis timing in relation to the first surgical incision on the incidence of SSI. METHODS: We prospectively monitored vancomycin prophylaxis timing and incidence of SSI in 2048 patients undergoing coronary bypass graft or valve replacement surgery. The timing of vancomycin was categorized into five groups based on the relation between the start of the infusion and the surgical cut time. Study hypotheses were tested using logistic analysis and further validated using a Heckman two-stage model. RESULTS: The incidence of SSI were lowest in the 176 patients given vancomycin between 16 and 60 min before the surgical incision (3.4%) compared with 15 patients given vancomycin between 0 and 15 min [26.7%; relative risk (RR): 7.8; 95% CI: 2.5-24.7], 888 patients given vancomycin between 61 and 120 min (7.7%; RR: 2.2; 95% CI: 0.99-5.09), 700 patients given vancomycin between 121 and 180 min (6.9%; RR: 2.0; 95% CI: 0.87-4.62) or 269 patients given vancomycin >180 min (7.8%; RR: 2.3; 95% CI: 0.94-5.56) (P = 0.0119 by chi(2) analysis). Stepwise logistic regression analysis and a Heckman two-stage model confirmed that vancomycin administration between 16 and 60 min before the first surgical incision was associated with the lowest incidence of SSI. CONCLUSIONS: Vancomycin administration within 16-60 min before the first surgical incision reduced the risk of SSI in cardiac surgery patients.