Potential Predictors of Poor Prognosis among Severe COVID-19 Patients: A Single-Center Study.

BACKGROUND: Timely detection of the progression of the highly contagious coronavirus disease (COVID-19) is of utmost importance for management and intervention for patients in intensive care (ICU). AIM: This study aims to better understand this new infection and report the changes in the various laboratory tests identified in critically ill patients and associated with poor prognosis among COVID-19 patients admitted to the ICU. METHODS: This was a retrospective study that included 160 confirmed SARS-CoV-2-positive patients. RESULTS: Elevated serum ferritin, D-dimer, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and nonconjugated bilirubin levels were present in 139 (96%), 131 (96%), 107 (68%), 52 (34%), and 89 (70%) patients, respectively. Renal parameters were abnormal in a significant number of cases with elevated creatinine and blood urea nitrogen in 93 (62%) and 102 (68%) cases, respectively. Hematological profiles revealed lower red blood cell count, hemoglobin, eosinophils, basophils, monocytes, and lymphocytes in 90 (57%), 103 (65%), 89 (62%), 105 (73%), 35 (24%), and 119 (83%) cases, respectively. The neutrophil count was found to increase in 71.3% of the cases. There was significantly higher mortality (83%) among patients older than 60 years (p=0.001) and in female patients (75%) (p=0.012). Patients with lung diseases had a poor outcome compared to patients with other comorbidities (p=0.002). There was a significant association between elevated D-dimer levels and increased mortality (p=0.003). Elevated levels of AST, creatinine, blood urea nitrogen, and bilirubin were significantly associated with unfavorable outcomes. CONCLUSION: Different parameters can be used to predict disease prognosis, especially the risk of poor prognosis. Accurate diagnosis and monitoring of disease progression from the early stages will help in reducing mortality and unfavorable outcomes.

New Classification System for Cleft Alveolus: A Computed Tomography-based Appraisal.

AIM: The present study proposed a new classification system based on computed tomography (CT) scan appraisal; this enables the surgeon to identify the extent of the defect and helps to execute the proper treatment plan. BACKGROUND: Various terminologies and classifications were proposed to understand developmental defects. But none of the existing classifications/nomenclatures used the preoperative radiographic evaluation (i.e., computed tomography scan-CT scan) in the management and prognosis. Various treatments were advocated and practiced successfully for the surgical correction of lip and palate. MATERIALS AND METHODS: The available CT scans from archives of the Department of Radiology and Oral and Dental Surgery were evaluated (retrospectively) for cleft alveolus and its morphology as per the proposal. The English language literature was searched in the MEDLINE database without date restriction to revise existing literature on numerous classification systems/nomenclatures using MeSH keywords related to cleft lip, palate, alveolus, developmental disturbance, facial clefts, and classification. Existing classification systems were revisited with a note on the drawbacks. After careful examination of morphological patterns of all clefts, the new CT scan-based alveolar cleft classification is proposed depending on the extent of cleft. RESULTS: The literature revealed a total of twenty-nine classifications of cleft lip and palate starting from the year 1922 to the year 2015, but none exclusively classified the cleft alveolus based on CT scan observations. The observation of three thousand CT scans showed five types of cleft alveolus, depending on the extent of involvement. CONCLUSION: The CT scan-based classification is essential to the surgeon for successful surgical planning of cleft alveolus. The proposed classification is clinically relevant in this digital era for relating surgical outcomes. The three-dimensional viewing of a defect is essential for the surgeon for virtual planning. This paper provides a CT scan-based classification for universal acceptance in this era of digital technology, and CT scan aids in achieving these goals. CLINICAL SIGNIFICANCE: The new proposal is based on preoperative evaluation of cleft using a CT scan. CT scan imaging provides a clear picture of the cleft in three dimensions for the operating surgeon. Advanced technology-enhanced surgical management modalities like CAD/CAM guided templates to support graft for successful management. The classification system will help the medical and surgical fraternity in various aspects. The three-dimensional modeling of defect and printing of a defect model using additive manufacturing technology helps the surgeon for presurgical visualization and virtual planning in a better way. This strategy of defect classification using a CT scan will help obtain better clinical outcomes and patient satisfaction.

Metformin and thymoquinone co-treatment enhance 5-fluorouracil cytotoxicity by suppressing the PI3K/mTOR/HIF1α pathway and increasing oxidative stress in colon cancer cells.

This study investigated the chemotherapeutic effects of 5-fluorouracil (5-FU), metformin (Met), and/or thymoquinone (TQ) single/dual/triple therapies in the HT29, SW480 and SW620 colon cancer (CRC) cell lines. Cell cycle/apoptosis were measured by flow cytometry. The gene and protein expression of apoptosis (PCNA/survivin/BAX/Cytochrome-C/Caspase-3) and cell cycle (CCND1/CCND3/p21/p27) molecules, the PI3K/mTOR/HIF1α oncogenic pathway, and glycolysis regulatory enzymes were measured by quantitative-PCR and Western blot. Markers of oxidative stress were also measured by colorimetric assays. Although all treatments induced anti-cancer effects related to cell cycle arrest and apoptosis, the triple therapy showed the highest pro-apoptotic actions that coincided with the lowest expression of CCND1/CCND3/PCNA/survivin and the maximal increases in p21/p27/BAX/Cytochrome-C/Caspase-3 in all cell lines. The triple therapy also revealed the best suppression of the PI3K/mTOR/HIF1α pathway by increasing its endogenous inhibitors (PTEN/AMPKα) in all cell lines. Moreover, the lowest expression of lactate dehydrogenase and pyruvate dehydrogenase kinase-1 with the highest expression of pyruvate dehydrogenase were seen with the triple therapy, which also showed the highest increases in oxidative stress markers (ROS/RNS/MDA/protein carbonyl groups) alongside the lowest antioxidant levels (GSH/CAT) in all cell lines. In conclusion, this is the first study to reveal enhanced anti-cancer effects for metformin/thymoquinone in CRC that were superior to all monotherapies and the other dual therapies. However, the triple therapy approach showed the best tumoricidal actions related to cell cycle arrest and apoptosis in all cell lines, possibly by enhancing oxidative glycolysis and augmenting oxidative stress through stronger modulation of the PI3K/mTOR/HIF1α oncogenic network.

Antibacterial dimeric copper(II) complexes with chromone-derived compounds.

A new series of six chromone-derived compounds and their Cu(II) complexes have been synthesized and characterized by their physical, spectral and analytical data. The ligands and their Cu(II) complexes were screened for their in vitro antibacterial activity against four Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri) and two Gram-positive (Bacillus subtilis, Staphylococcus aureus) bacterial strains by agar-well diffusion method. The ligands were found to exhibit either no or low-to-moderate activities against one or more bacterial species whereas, the Cu(II) complexes exhibited moderate-to-high activity. The ligands which were inactive before complexation became active upon complexation with the Cu(II) metal ion and less active became more active.

4-{[(E)-2,3-Dihy-droxy-benzyl-idene]amino}-N-(5-methyl-1,2-oxazol-3-yl)benzene-sulfonamide.

In the title compound, C(17)H(15)N(3)O(5)S, the 2,3-dihy-droxy-benzaldehyde unit is oriented at a dihedral angles of 16.83 (10) and 78.87 (6)° with the anilinic and 5-methyl-1,2-oxazol-3-amine groups, respectively. An S(6) loop exists due to intramolecular O-H⋯N hydrogen bonding. In the crystal, inversion dimers with R(2) (2)(8) rings are formed due to N-H⋯N hydrogen bonding between the 5-methyl-1,2-oxazol-3-amine groups. These dimers are inter-linked by O-H⋯O hydrogen bonds, forming chains along [101] and resulting in R(2) (2)(26) rings. π-π inter-actions occur between the central benzene rings with a centroid-centroid distance of 3.7928 (16) Å.

2-[(E)-({4-[(4,6-Dimethyl-pyrimidin-2-yl)sulfamo-yl]phen-yl}iminio)meth-yl]-6-hy-droxy-phenolate.

The title compound, C(19)H(18)N(4)O(4)S, exists as a zwitterion in the solid state, with nominal proton transfer from a phenol group to the imine N atom. The 2,3-dihy-droxy-benzaldehyde fragment is oriented at a dihedral angle of 35.51 (11)° to the adajacent aniline group and makes a dihedral angle of 76.99 (6)° with the 4,6-dimethyl-pyrimidin-2-amine group. Intra-molecular O-H⋯O and N-H⋯O hydrogen bonds close S(5) and S(6) rings, respectively; the same O atom accepts both bonds. In the crystal, polymeric chains along [001] are formed from mol-ecules joined end-to-end by N-H⋯O and O-H⋯N hydrogen bonds; these feature R(2) (3)(6) loops. The polymeric chains are linked by C-H⋯O inter-actions and there are π-π inter-actions between the pyrimidine rings with a centroid-centroid distance of 3.446 (2) Å.

(2Z)-N-(2-Chloro-benz-yl)-2-(2-oxo-2,3-dihydro-1H-indol-3-yl-idene)hydrazinecarbothio-amide.

In the title compound, C(16)H(13)ClN(4)OS, the isatin ring system is oriented at dihedral angles of 10.60 (7) and 72.60 (3)° with respect to the thio-semicarbazide and 2-chloro-benzyl groups, respectively. The near planarity of the isatin and thio-semicarbazide groups [r.m.s. deviations of 0.0420 and 0.0163 Å, respectively] is reinforced by intra-molecular N-H⋯O and N-H⋯N hydrogen bonds, which generate S(6) and S(5) rings, respectively. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(8) loops. Aromatic π-π stacking inter-actions between the centroids of heterocyclic five-membered and benzene rings [distance = 3.6866 (11) Å] are also observed.

Thermal degradation kinetics and pyrolysis GC-MS study of curcumin.

The objective of this work was to study kinetics of thermal degradation of curcumin in ambient-1023 K range and identify degradation products by GC-MS. No weight loss was observed up to ∼470 K and two major weight losses occurred beyond this. Sixteen degradation products were identified by GC-MS. Pharmacological properties, including LD50, LC50, gastrointestinal absorption, blood-brain barrier permeation and effect on cytochromes, of the products were calculated using standard software. The LD50 values indicated that the degradation products are more toxic than curcumin. All the decomposition products, except 2-methyl-6-(4-methylphenyl)-hept-2-en-4-one, have the potential to cross the blood-brain barrier that can affect brain functions. Twelve of the compounds showed the potential to inhibit the metabolism of xenobiotics and all the compounds appeared to be non-inhibitors of CYP2C9 and CYP3A4 in contrast to curcumin. Thus, this study suggests that the food materials containing curcumin when heated beyond 470 K will produce toxic substances.

Synthesis of gold and silver nanoparticles by use of arabinoglucan from Lallemantia royleana.

Highly stable gold and silver nanoparticles were synthesized by use of an arabinoglucan from Lallemantia royleana seeds without additional use of reducing or stabilizing agents. The mechanism involved the reduction potential of the hemicellulose as verified by cyclic voltammetry. The arabinoglucan used was substantially free from ferulic acid and phenolic content, suggesting the inherent reducing potential of arabinoglucan for gold and silver ions. The synthesized nanoparticles exhibited surface plasmon resonance maxima at 515 nm (gold) and 397 nm (silver) corresponding to sizes of 10 nm and 8 nm, respectively. The zeta potential values were -24.1 mV (gold) and -22.3 mV (silver). The silver nanoparticles showed potential for application in surface-enhanced Raman spectroscopy. Gold nanoparticles were found to be non-toxic, whereas silver nanoparticles exhibited dose-dependent biological activities and found to be cytotoxic against brine shrimps and HeLa cell lines and the tumours caused by A. tumefaciens.

Mechanochemical synthesis and in vitro anti-Helicobacter pylori and uresase inhibitory activities of novel zinc(II)-famotidine complex.

The mechanochemical synthesis and characterization of a zinc complex with famotidine is described. The complex was characterized by microanalysis and a number of spectroscopic techniques. The complex was of M:L dihydrate type. Derivatization of famotidine with zinc appears to enhance the activity of the drug by inhibiting the growth of Helicobacter pylori (two reference and 34 clinical isolates). The complex inhibited the growth of H. pylori in an MIC range of 1-8 microg mL(-1). The anti-H. pylori activity of the zinc-famotidine complex against antibiotic-resistant strains was nearly comparable to that of antibiotic-susceptible strains. The complex was found to be far less toxic than the parent drug, as demonstrated by its higher LD(50) value. In the human urease enzyme inhibition assay the complex exhibited significant inhibition. The new complex appears to be more useful in eradicating both the antibiotic-susceptible and antibiotic-resistant strains of H. pylori.

Comparative study of pharmaceutical properties of some new derivatives of sulfamethoxazole.

This paper reports the changes in various physical properties associated with the derivatization of sulfamethoxazole. The properties studied include moisture content, crystallanity, particle size distribution, porosity, flow, compressibility and compactability. It was found that the derivatives, salicylidene-sulfamethoxazole-Zn(II) • H2O and salicylidene-sulfamethoxazole-Cu(II) • H2O are crystalline substances. The moisture content was found to be highest in salicylidene-sulfamethoxazole-Zn(II) • H2O followed by salicylidene-sulfamethoxazole-Cu(II) • H2O and sulfamethoxazole. The copper complex contained only chemically bonded water, whereas the zinc complex contained both bonded and absorbed water, which affected the strength of the tablets prepared from the three materials accordingly. The particle size decreased on derivatization and complexation with metal ions and the trend was: sulfamethoxazole > salicylidene-sulfamethoxazole-Cu(II) • H2O > salicylidene-sulfamethoxazole-Zn(II) • H2O. This trend was represented by better compactability shown by salicylidene-sulfamethoxazole-Cu(II) • H2O and salicylidene-sulfamethoxazole-Zn(II) • H2O as compared with sulfamethoxazole. Salicylidene-sulfamethoxazole-Zn(II) • H2O had the highest porosity followed by salicylidene-sulfamethoxazole-Cu(II) • H2O, and sulfamethoxazole; this resulted in better compressibility behavior of the complexes. Thus it was observed that salicylidene-sulfamethoxazole-Cu(II) • H2O and salicylidene-sulfamethoxazole-Zn(II) • H2O formed stronger compacts. The values of angle of repose and flow rate show better flow properties for salicylidene-sulfamethoxazole-Cu(II) • H2O as compared with sulfamethoxazole and salicylidene-sulfamethoxazole-Zn(II) • H2O. It was concluded that derivatization substantially changed the pharmaceutical properties, which have important role to play in formulation of solid dosage form.

4-(2-Fluoro-phen-yl)-1-(2-oxoindolin-3-yl-idene)thio-semicarbazide.

The title compound, C(15)H(11)FN(4)OS, is almost planar, the dihedral angle between the aromatic ring systems being 5.00 (13)°. The conformation is stabilized by intra-molecular N-H⋯N and N-H⋯O hydrogen bonds, which generate S(5) and S(6) rings, respectively. N-H⋯F and C-H⋯S inter-actions also occur. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds occur, generating R(2) (2)(8) loops.

4-(5-Chloro-2-methyl-phen-yl)-1-[2-oxo-5-(trifluoro-meth-oxy)indolin-3-yl-idene]thio-semicarbazide.

The asymmetric unit of the title compound, C(17)H(12)ClF(3)N(4)O(2)S, contains two mol-ecules, which differ in their planarity and hydrogen bonding. In one mol-ecule, the 2-oxoindolin (C(8)/N/O A), thio-semicarbazide (N(3)/C/S B) and 5-chloro-2-methyl-phenyl (C(7)/Cl C) units are planar with r.m.s. deviations of 0.0110, 0.0173 and 0.0259 Å, respectively. The dihedral angles A/B, B/C and A/C are 1.74 (15), 40.70 (13) and 41.00 (11)°, respectively. In the other mol-ecule the deviations are 0.0455, 0.0007 and 0.0143 Å, respectively, and the dihedral angles are 5.01 (14), 4.53 (16) and 3.38 (13)°, respectively. In both mol-ecules, intra-molecular N-H⋯N and N-H⋯O hydrogen bonds form S(5) and S(6) ring motifs, respectively and C-H⋯S interactions occur. In one of the molecules, an intramolecular C-H⋯F interaction is also present. In the crystal, the mol-ecules are linked by N-H⋯O, C-H⋯F, C-H⋯O and N-H⋯S hydrogen bonding, forming a polymeric network.

4-(3-Methoxy-phen-yl)-1-(2-oxoindolin-3-yl-idene)thio-semicarbazide.

In the title compound, C(16)H(14)N(4)O(2)S, intra-molecular N-H⋯N hydrogen bonding forms an S(5) ring, whereas N-H⋯O and C-H⋯S inter-actions complete S(6) ring motifs. In the crystal, mol-ecules form inversion dimers due to N-H⋯O inter-actions. The dimers are inter-linked through N-H⋯S hydrogen bonds and π-π inter-actions occur with a centroid-centroid distance of 3.8422 (11) Šbetween the meth-oxy-containing benzene ring and the five-membered heterocyclic ring.

4-(3-Nitro-phen-yl)-1-(2-oxoindolin-3-yl-idene)thio-semicarbazide.

In the title compound, C(15)H(11)N(5)O(3)S, intra-molecular N-H⋯N hydrogen bonding forms an S(5) ring motif, whereas N-H⋯O and C-H⋯S inter-actions type complete S(6) ring motifs. The 2-oxoindoline and 3-methoxy-phenyl rings are almost planar, with r.m.s. deviations of 0.0178 and 0.0149 Å, respectively, and form a dihedral angle of 33.59 (3)°. In the crystal, mol-ecules are inter-linked through the nitro groups in an end-to-end fashion via N-H⋯O and C-H⋯O inter-actions.

4-(2-Ethyl-phen-yl)-1-(2-oxoindolin-3-yl-idene)thio-semicarbazide.

The title compound, C(17)H(16)N(4)OS, is stabilized in the form of a two-dimensional polymeric network due to inter-molecular N-H⋯S and N-H⋯O hydrogen bonds. An intra-molecular N-H⋯N hydrogen bond forms an S(5) ring, whereas inter-actions of the N-H⋯O and C-H⋯S types complete S(6) ring motifs. π-π inter-actions with a centroid-centroid distance of 3.6514 (10) Šare found between the ethyl-substituted benzene ring and the heterocyclic ring of the isatin derivative.

1-[2-Oxo-5-(trifluoro-meth-oxy)indolin-3-yl-idene]-4-[4-(trifluoro-methyl)-phen-yl]thio-semicarbazide.

In the title compound, C(17)H(10)F(6)N(4)O(2)S, an intra-molecular N-H⋯N hydrogen bonds forms an S(5) ring whereas N-H⋯O and C-H⋯S inter-actions complete S(6) ring motifs. The dihedral angle between the fused ring system and the phenyl ring is 6.68 (8)°. In the crystal, the mol-ecules are dimerized due to N-H⋯O inter-actions. π-π inter-actions are present between the benzene rings [centroid-centroid distance = 3.6913 (15) Å] and between the five membered ring and the trifluoro-meth-yl)phenyl ring [centroids-centroid distance = 3.7827 (16) Å]. One of the trifluoro-meth-oxy F atoms is disordered over two sites with occupancy ratio of 0.76 (3):0.24 (3). The F atoms of the p-trifluoro-methyl substituent are disordered over three sets of sites with an occupancy ratio of 0.70 (2):0.152 (11):0.147 (13).

1-(2-Oxoindolin-3-yl-idene)-4-[2-(trifluoro-meth-oxy)phen-yl]thio-semi-carbazide.

The crystal structure of the title compound, C(16)H(11)F(3)N(4)O(2)S, is stabilized in the form of polymeric chains by N-H⋯O inter-actions. In the mol-ecular structure, two S(5) ring motifs are formed by intra-molecular N-H⋯N and N-H⋯O hydrogen bonding and two S(6) rings are present due to N-H⋯O and C-H⋯S inter-actions. π-π inter-actions are present with distances of 3.2735 (17), 3.563 (2) and 3.664 (4)/3.688 (3) Šbetween the centroids of the heterocyclic rings, between the centroids of the heterocyclic ring and trifluoro-meth-oxy-substituted phenyl ring, and between the centroids of the trifluoro-meth-oxy-substituted phenyl rings, respectively. The trifluoro-meth-oxy-phenyl group is disordered over two sites with an occupancy ratio of 0.642 (10):0.358 (10).

Synthesis and Biodistribution Study of Biocompatible 198Au Nanoparticles by use of Arabinoxylan as Reducing and Stabilizing Agent.

Radioactive gold-198 is a useful diagnostic and therapeutic agent. Gold in the form of nanoparticles possesses even more exciting properties. This work aimed at arabinoxylan-mediated synthesis and biodistribution study of radioactive gold nanoparticles (198AuNPs). The particles were synthesized by mixing suspension of arabinoxylan with H198AuCl4 without use of any additional reducing and stabilizing agents. An aqueous suspension of arabinoxylan was added to a H198AuCl4 solution, which resulted in reduction of Au3+ to 198AuNPs. Biodistribution was studied in vitro and in rabbit. The particles having exceptional stability were readily formed. Highest radioactivity was recorded in spleen after 3 h followed by liver, heart, kidney, and lungs after i.v. administration. After 24 h, the activity was not detectable in the spleen; it accumulated in the liver. However, after oral administration, the activity mainly accumulated in the colon. In serum proteins, the distribution was α1-globulin 6.5%, α2-globulin ~ 2%, ß-globulin ~ 1%, γ-globulin 0.7%, and albumin 0.7% of the administered dose. This indicates a low protein binding implying high bioavailability of the particles. The cytotoxicity study showed that the particles were inactive against HeLa cell line and Agrobacteriumtumefaciens. Highly stable 198AuNPs reported in this work have the potential for targeting the colon. They show affinity for globulins, the property that can be used in the study of the immune system.

Correction to: Synthesis and Biodistribution Study of Biocompatible 198Au Nanoparticles by use of Arabinoxylan as Reducing and Stabilizing Agent.

The original version of this article unfortunately contained a mistake.