Convalescent plasma therapy in patients with COVID-19

IntroductionPassive antibody therapy has been used to immunize vulnerable people against infectious agents. In this study, we aim to investigate the efficacy of convalescent plasma (CP) in the treatment of severe and critically ill patients diagnosed with COVID-19.MethodThe data of severe or critically ill COVID-19 patients who received anti-SARS-CoV-2 antibody-containing CP along with the antiviral treatment (n = 888) and an age-gender, comorbidity, and other COVID-19 treatments matched severe or critically ill COVID-19 patients at 1:1 ratio (n = 888) were analyzed retrospectively.ResultsDuration in the intensive care unit (ICU), the rate of mechanical ventilation (MV) support and vasopressor support were lower in CP group compared with the control group (p = 0.001, p = 0.02, p = 0.001, respectively). The case fatality rate (CFR) was 24.7 % in the CP group, and it was 27.7 % in the control group. Administration of CP 20 days after the COVID-19 diagnosis or COVID-19 related symptoms were associated with a higher rate of MV support compared with the first 3 interval groups (≤5 days, 6?10 days, 11?15 days) (p=0.001).ConclusionCP therapy seems to be effective for a better course of COVID-19 in severe and critically ill patients.     

Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing,docking and molecular dynamics simulation study

The outbreak of novel coronavirus, SARS-CoV-2, has infected more than 36 million people and caused approximately 1 million deaths around the globe as of 9 October 2020. The escalating outspread of the virus and rapid rise in the number of cases require the instantaneous development of effectual drugs and vaccines. Presently, there are no approved drugs or vaccine available to treat the infection. In such scenario, one of the propitious therapeutic approaches against viral infection is to explore enzyme inhibitors amidst natural compounds, utilizing computational approaches aiming to get products with negligible side effects. In the present study, the inhibitory prospects of ilimaquinone (marine sponge metabolite) were assessed in comparison with hydroxychloroquine, azithromycin, favipiravir, ivermectin and remdesivir at the active binding pockets of nine different vital SARS-CoV-2 target proteins (spike receptor binding domain, RNA-dependent RNA polymerase, Nsp10, Nsp13, Nsp14, Nsp15, Nsp16, main protease, and papain-like-protease), employing an in silico molecular interaction based approach. In addition, molecular dynamics (MD) simulations of the SARS-CoV-2 papain-like protease (PLpro)–ilimaquinone complex were also carried out to calculate various structural parameters including root mean square fluctuation (RMSF), root mean square deviation (RMSD), radius of gyration (R_g) and hydrogen bond interactions. PLpro is a promising drug target, due to its imperative role in viral replication and additional function of stripping ubiquitin and interferon-stimulated gene 15 (ISG15) from host-cell proteins. In light of the possible inhibition of all vital SARS-CoV-2 target proteins, our study has emphasized the importance to study in depth ilimaquinone actions in vivo.

Inhibitory potential of ilimaquinone (marine sponge metabolite) against nine essential SARS-CoV-2 target proteins, employing a molecular interaction and dynamics simulation approach.     

Development of bimetallic nickel-based catalysts supported on activated carbon for green fuel production

In this work, the catalytic deoxygenation of waste cooking oil (WCO) over acid–base bifunctional catalysts (NiLa, NiCe, NiFe, NiMn, NiZn, and NiW) supported on activated carbon (AC) was investigated. A high hydrocarbon yield above 60% with lower oxygenated species was found in the liquid product, with the product being selective toward n-(C₁₅ + C₁₇)-diesel fractions. The predominance of n-(C₁₅ + C₁₇) hydrocarbons with the concurrent production of CO and CO₂, indicated that the deoxygenation pathway proceeded via decarbonylation and decarboxylation mechanisms. High deoxygenation activity with better n-(C₁₅ + C₁₇) selectivity over NiLa/AC exposed the great synergistic interaction between La and Ni, and the compatibility of the acid–base sites increased the removal of oxygenated species. The effect of La on the deoxygenation reaction performance was investigated and it was found that a high percentage of La species would be beneficial for the removal of C–O bonded species. The optimum deoxygenation activity of 88% hydrocarbon yield with 75% n-(C₁₅ + C₁₇) selectivity was obtained over 20% of La, which strongly evinced that La leads to a greater enhancement of the deoxygenation activity. The NiLa/AC reusability study showed consistent deoxygenation reactions with 80% hydrocarbon yield and 60% n-(C₁₅ + C₁₇) hydrocarbon selectivity within 6 runs.

In this work, the catalytic deoxygenation of waste cooking oil (WCO) over acid–base bifunctional catalysts (NiLa, NiCe, NiFe, NiMn, NiZn, and NiW) supported on activated carbon (AC) was investigated.     

Design and formulation of polymeric nanosponge tablets with enhanced solubility for combination therapy

Three drugs namely caffeine, paracetamol, and aceclofenac are commonly used for treating various acute and chronic pain related ailments. These 3 drugs have varied solubility profiles, and formulating them into a single tablet did not have the desired dissolution profile for drug absorption. The objective of the present research was to tailor the drug release profile by altering drug solubility. This was achieved by loading the drug into nanosponges. Here, three-dimensional colloidal nanosponges were prepared using β-cyclodextrin with dimethyl carbonate as a cross-linker using the hot-melt compression method. The prepared nanosponges were characterized by FTIR, ¹H NMR spectroscopy, DSC, XRPD studies and SEM. The FTIR and DSC results obtained indicated polymer-drug compatibility. The ¹H NMR spectroscopy results obtained indicated the drug entrapment within nanosponges with the formation of the inclusion complex. XRPD studies showed that the loaded drug had changed crystalline properties altering drug solubility. SEM photographs revealed the porous and spongy texture on the surface of the nanosponge. Box–Behnken experimental design was adopted for the optimization of nanosponge synthesis. Among the synthesized nanosponges containing paracetamol, aceclofenac and caffeine, batch F3–P31, F3–A31 and F3–C31 were considered optimized. Their particle size was 185, 181 and 199 nm with an entrapment efficiency of 81.53, 84.96, and 89.28% respectively. These optimized nanosponges were directly compressed into tablets and were studied for both pre and post-compression properties including in vitro drug release. The prepared tablet showed desired drug dissolution properties compared to the pure drug. The above outcomes indicated the applicability of nanosponges in modulating the drug release with varied solubility for combination therapy.

Polymeric nanosponges as potential carriers for successful combination therapy of poorly soluble drugs (paracetamol, aceclofenac, caffeine).     

Study of Surgical Emergencies of Tubercular Abdomen in Developing Countries

To study the various modes of presentation, diagnosis, and management of surgical emergencies of tubercular abdomen. This prospective study of surgical emergencies of tubercular abdomen was conducted in 50 patients who attended our surgical emergency from 2006 to 2008. Patients were evaluated thoroughly with history, physical examination, routine investigations, and special investigations such as ELISA, PCR, barium studies of gastrointestinal tract, and diagnostic laparoscopy as required and managed with medical and surgical treatment as necessary. The most of patients were from rural areas, in the third to sixth decades with slight male preponderance. Abdominal pain, vomiting, and constipation were commonest presenting symptoms. About 20 % patients had history of pulmonary tuberculosis and 16 % patients presented with ascites. PCR for blood and ascitic fluid was positive in 72 and 87.5 % patients, respectively. About 24 % patients were managed nonoperatively and responded to ATT. About 76 % patients needed surgery among which one-fifth of patients were operated in emergency. Procedures like adhesiolysis of gut (47.3 %), strictureplasty (10.5 %), resection anastomosis (5.2 %), right hemicolectomy (5.2 %), and ileotransverse anastomosis (7.8 %) were performed in 30 patients and peritoneal biopsy and lymph node biopsy in the remaining 8 patients. Both medically and surgically managed patients were put on antitubercular therapy. Abdominal tuberculosis is a disease of middle-aged rural people, presenting commonly with abdominal pain and vomiting with right lower abdominal tenderness. PCR (blood and ascites) for tuberculosis is much more sensitive than IgM ELISA (blood and ascites). The most of patients required surgical procedures and all patients responded dramatically to antitubercular therapy symptomatically with increase in the hemoglobin level and decrease in ESR.     

Development of a conceptual model of oral health for malocclusion patients

Objectives:To provide an empirical test of the applicability of Locker''s conceptual model of oral health for malocclusion patients, and to suggest alternative models of the effect of malocclusion on well-being.Materials and Methods:Data from a survey of 323 adolescents attending for orthodontic treatment were analyzed to develop a new oral health model for malocclusion patients. Oral health–related quality of life (OHRQoL) was measured using the 14-item Oral Health Impact Profile; malocclusion was measured using the Dental Health Component (DHC) of the Index of Orthodontic Treatment Need (IOTN). Using structural equation modeling, the relationship between conceptual domains in Locker''s model was explored and three models of their interrelationship tested for goodness of fit.Results:Fit indexes for Locker''s model indicated that it did not fit the data well. Therefore, a modified model was developed to incorporate additional paths between other levels to better fit the data. The best fit was provided by a model in which the direct effects of malocclusion on pain, discomfort, and handicapping—and the direct effect of pain on disability—were removed. A direct effect of functional limitation on disability was allowed. The modified Oral Health Impact Profile model proved to be a good fit to the data (root mean square error of approximation  =  0.069).Conclusion:The pathways identified in Locker''s (1988) conceptual model of oral health may not be appropriate for describing the relationships between OHRQoL constructs in individuals with malocclusion. An alternative model is proposed.