Role of procalcitonin, interleukin-6 and interleukin-10 as a predictive marker for the use of perioperative steroid in maxillofacial trauma patients.

Maxillofacial trauma often brings significant challenges for surgeons in terms of preoperative oedema. Steroids offer oedema reduction, yet potentially increase the risks of postoperative infection. This study explores procalcitonin (PCT), as a marker for bacterial infection risk, and interleukins IL-6 and IL-10, which respectively signify pro-inflammatory and anti-inflammatory responses, as potential indicators of infection and inflammation in these trauma cases and thereby aid in refining perioperative guidelines for the use of steroids. A prospective study was conducted at a tertiary public hospital in India from 2019 to 2022 on patients >18 years with facial trauma. After specific exclusions, patients were randomised into steroid (Group A) and non-steroid (Group B) groups. Various parameters including oedema, PCT, IL-6, and IL-10 levels were measured and analysed using SPSS software. Out of 80 patients, 44 were in Group A and 36 in Group B. Post-24 hours, Group A showed significant oedema reduction, with 25 patients displaying a decline to mild oedema, versus 10 patients in Group B (p = 0.034). However, Group A witnessed a higher infection risk, with 20 patients showing positive wound cultures versus three in Group B. Subgroup analysis revealed a link between higher PCT levels and infections (p = 0.039). Additionally, Group A showed less intraoperative bleeding and reduced operating time. While perioperative steroids mitigate swelling, they might increase postoperative infection risk. Elevated PCT levels indicate potential wound infections, suggesting those patients should avoid perioperative steroids. IL-6 and IL-10 trends during perioperative phases can predict pronounced oedema outcomes.

Selective vitamins as potential options for dietary therapeutic interventions: In silico and In vitro insights from mutant C terminal fragment of FGA.

We have used an integrated computational approach to explore the role of vitamin C and vitamin D in preventing aggregation of Fibrinogen A alpha-chain (FGActer) protein responsible for renal amyloidosis. We modelled structures of E524K / E526K mutants of FGActer protein and examined the potential interactions of these mutants with vitamin C and vitamin D3. Interaction of these vitamins at the amyloidogenic site may prevent the intermolecular interaction required for amyloid formation. The binding free energy values of vitamin C and vitamin D3 for E524K FGActer and E526K FGActer are - 67.12 ± 30.46 kJ/mole and - 79.45 ± 26.12 kJ/mol, respectively. Experimental studies using Congo red absorption, aggregation index studies and AFM imaging show encouraging results. The AFM images of E526K FGActer contained more extensive and higher protofibril aggregates, whereas, in the presence of vitamin D3, small monomeric and oligomeric aggregates were observed. Overall, the works provide interesting results about vitamin C and D role in preventing renal amyloidosis.

Potential of hydroethanolic leaf extract of Ocimum sanctum in ameliorating redox status and lung injury in COPD: an in vivo and in silico study.

Oxidative stress and inflammation are hypothesised as the main contributor for Chronic Obstructive Pulmonary Disease (COPD). Cigarette smoke (CS), a major cause of COPD leads to inflammation resulting in recruitment of neutrophils and macrophages which are rich sources of oxidants. Activation of these cells produces excess oxidants and depletes antioxidants resulting in stress. Presently, effective drug for COPD is limited; therefore, novel compounds from natural sources, including plants are under exploration. The present study aims to investigate the protective effect of Ocimum sanctum leaf extract (OLE) in CS - induced model of COPD. Exposure to CS was performed thrice a week for 8 weeks and OLE (200 mg/kg and 400 mg/kg) was administered an hour before CS exposure. Control group (negative control) were exposed to ambient air while COPD group was exposed to CS (positive control). Administration of OLE doses reduced inflammation, decreased oxidant concentration and increased antioxidant concentration (p < 0.01). Molecular docking studies between the major phytocompounds of OLE (Eugenol, Cyclohexane and Caryophyllene) and antioxidant enzymes Superoxide dismutase (SOD), Catalase, Glutathione peroxidase (GPx), Glutathione reductase (GR) and Glutathione S Transferase (GST) showed strong binding interaction in terms of binding energy. In vivo and in silico findings for the first time indicates that OLE extract significantly alleviates oxidative stress by its potent free radical scavenging property and strong interaction with antioxidant enzymes. OLE extract may prove to be a therapeutic option for COPD prevention and treatment.

Immediate autonomic changes during right nostril breathing and left nostril breathing in regular yoga practitioners.

BACKGROUND: The ancient Indian science of Yoga makes use of voluntary regulation of breathing to make respiration rhythmic and calm the mind. This practice is called pranayama. Nadisuddhi pranayama means "purification of subtle energy paths," inhalation and exhalation are through alternative nostrils for successive respiratory cycles. Surya Anuloma-Viloma pranayama means "heat generating breathing particle" when the respiratory cycle of inhalation and exhalation is completed through the right nostril exclusively. When completed through the left nostril alone, the practice is called "Chandra Anuloma-Viloma pranayama," which means a heat-dissipating or cooling liberating practice. We compared the effect of right nostril breathing (RNA) and left nostril breathing (LNB) pranayama on heart rate variability. MATERIALS AND METHODS: The study was conducted at the Department of Physiology at an institute of national importance, after obtaining necessary ethical approvals from the Institutional Ethics Committee. Twenty healthy kriya yogi volunteers (mean age: 44 years), who are regular practitioners for the last 10-20 years, were inducted into the study. RNB pranayama starts with closing the right nostril with the thumb of the left hand followed by exhalation through the right nostril and inhaling slowly through the same nostril. This forms one round of RNB pranayama. In contrast, inhalation through the left nostril and exhalation through the right nostril exclusively is called chandrabhedana pranayama (chandrabhedana means moon-piercing breath in Sanskrit) with a similar variation called Chandra Anuloma-Viloma pranayama in which inhalation, as well as exhalation, is performed through the left nostril exclusively. The recording of electrocardiogram (ECG) for heart rate variability (HRV) analysis was taken by heart rate variability (Dinamika HRV-Advanced Heart Rate Variability Test System, Moscow, Russia). The resting and during readings of heart rate variability parameters were compared and post hoc analysis was done using Bonferroni and Holm multiple comparisons for repeated measures. RESULTS: Time domain parameters: Standard deviation of normal to normal RR intervals (SDNN) and root mean square of successive NN interval differences (RMSSD) were increased at a high level of statistical significance during both pranayama maneuvres. Frequency domain parameters: LF, LF/HF ratio increased significantly. Parasympathetic activity is represented by LF when the respiration rate is lower than 7 breaths per min or during taking a deep breath. Thus, when the subject is in a state of relaxation with slow and even breathing in both RNB-right nostril and Chandra-LNB, the LF values can be very high, indicating an increase in parasympathetic activity rather than an increase in sympathetic regulation. CONCLUSION: Our study is an acute study, where changes in HRV were seen after 5 min of RNB and LNB. However, statistically, there is not much difference in the immediate effects of the two pranayamas on heart rate variability in regular yoga practitioners.

Cerebrospinal Fluid Leucine-Rich Alpha-2 Glycoprotein (LRG) Levels in Children with Acute Bacterial Meningitis.

This study evaluated the diagnostic role of cerebrospinal fluid leucine-rich alpha-2 glycoprotein (CSF LRG) concentration in children with acute bacterial meningitis, and its role in differentiation from aseptic meningitis. CSF LRG concentration was measured by ELISA Kit of 50 children with bacterial meningitis, 16 aseptic meningitis, and 20 children with normal CSF; control. CSF LRG was significantly elevated (p < 0.001) in bacterial meningitis with a sensitivity, specificity, PPV, and NPV of 96%, 100%, 100%, and 90.9%, respectively at a cutoff of 110.0 ng/mL, based on ROC curve. At the same cutoff value, CSF LRG has sensitivity, specificity, PPV, and NPV of 96%, 75%, 92.3%, and 85.7%, respectively in differentiating bacterial from aseptic meningitis. However, sensitivity, specificity, PPV, and NPV at 139.9 ng/mL for differentiating between definite and probable bacterial meningitis were 88%, 75%, 79.1%, and 84.9%, respectively. CSF LRG should be used as a diagnostic biomarker for bacterial meningitis.

Vitamin C and Vitamin D3 show strong binding with the amyloidogenic region of G555F mutant of Fibrinogen A alpha-chain associated with renal amyloidosis: proposed possible therapeutic intervention.

G555F mutant of Fibrinogen A alpha-chain (FGA) is reported to be associated with kidney amyloidosis. In the current study, we have modelled the G555F mutant and examined the mutation's effect on the structural and functional level. We have also docked Vitamin C and D3 on the mutant's amyloidogenic region to identify if these vitamins can bind amyloidogenic regions. Further, we analyzed if they could prevent or modulate amyloid formation by stopping critical interactions in amyloidogenic regions in FGA. We used the wild type FGA model protein as a control. Our docking and molecular dynamics simulation results indicate stronger Vitamin D3 binding than Vitamin C to the amyloidogenic region of the mutant protein. The RMSD, radius of gyration, and RMSF values were higher for the G555F mutant than the FGA wild type protein. Overall, the results support these vitamins' potential as a therapeutic and anti-amyloidogenic agent for FGA renal amyloidosis.

Drugs repurposing against SARS-CoV2 and the new variant B.1.1.7 (alpha strain) targeting the spike protein: molecular docking and simulation studies.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) is responsible for the global COVID-19 pandemic and millions of deaths worldwide. In December 2020, a new alpha strain of SARS-CoV2 was identified in the United Kingdom. It was referred to as VUI 202012/01 (Alpha strain modelled under investigation, 2020, month 12, number 01). The interaction between spike protein and ACE2 receptor is a prerequisite for entering virion into the host cell. The present study is focussed on the spike protein of the SARS-COV 2, involving the comparison of binding affinity of new alpha strain modelled spike with previous strain spike (PDB ID:7DDN) using in silico molecular docking, dynamics and simulation studies. The molecular docking studies of the alpha strain modelled spike protein confirmed its higher affinity for the ACE2 receptor than the spike protein of the dominant strain. Similar computational approaches have also been used to investigate the potency of FDA approved drugs from the ZINC Database against the spike protein of new alpha strain modelled and old ones. The drug molecules which showed strong affinity for both the spike proteins are then subjected to ADME analysis. The overall binding energy of Conivaptan (-107.503 kJ/mol) and Trosec (-94.029 kJ/mol) is indicative of their strong binding affinities, well supported by interactions with critical residues.

Antioxidant and antibacterial activity of silver nanoparticles synthesized by Cestrum nocturnum.

BACKGROUND: Silver nanoparticles are toxic to bacteria and have widespread application in different research areas. OBJECTIVE: The aim of this study was to synthesize silver nanoparticles using an aqueous leaf extract of Cestrum nocturnum and to test its antioxidant and antibacterial activities. MATERIALS AND METHODS: The silver nanoparticles were synthesized by addition of 20 ml extract (8% w/v) with 180 ml silver nitrate solution (1 mM). The synthesis of silver nanoparticles was confirmed by UV-Vis spectrophotometer. The silver nanoparticles were characterized by X-ray diffractometer, Transmission Electron Microscope, Scanning Electron Microscope and Fourier Transform Infra-Red spectroscopy. The antioxidant property of silver nanoparticles was analyzed by the 2, 2-diphenyl-1-picrylhydrazyl, hydrogen peroxide, hydroxyl radical and superoxide radical scavenging methods. The bacteriostatic and bactericidal activity of silver nanoparticles against Escherichiacoli, Enterococcusfaecalis, and Salmonellatyphi was determined using bacterial growth inhibition method. The antibacterial sensitivity and Minimum Inhibitory Concentration (MIC) of silver nanoparticles was determined against the bacteria. RESULTS: The results confirmed that the silver nanoparticles synthesized by C.nocturnum extract were crystalline in nature, average particle size was 20 nm and were mostly spherical in shape. The antioxidant methods confirmed that the silver nanoparticles have more antioxidant activity as compared to vitamin C. The silver nanoparticles have strong antibacterial (maximum Vibrio cholerae and minimum E. faecalis) activity. The MIC value of silver nanoparticles was 16 µg/ml (Citrobacter), 4 µg/ml (E. faecalis), 16 µg/ml (S. typhi), 8 µg/ml (E. coli), 8 µg/ml (Proteusvulgaris), and 16 µg/ml (V. cholerae). CONCLUSION: Green synthesized silver nanoparticles have strong antioxidant and antibacterial activity due to the presence of bioactive molecules on the surface of silver nanoparticles.

Association of 4-basepair G-to-A transition in the 5'-untranslated region of ANKH gene with selected patients of primary knee osteoarthritis: A cross sectional study.

METHOD: A cohort study was carried out for a year to evaluate the presence of G-to-A transition in 5'-untranslated region of ankylosis human (ANKH) gene in Indian Khatri patients (closely resembling Europeans of primary knee osteoarthritis (OA), residing in Lucknow, India. RESULTS: In the total participants, 25 were Khatri primary knee OA patients (cases) residing in Lucknow and 101 were random blood donors' samples (controls) collected from a blood bank. All were studied for the abovementioned mutation using real-time polymerase chain reaction (RT-PCR). GG genotype was present in 72.3% of controls and 76% of Khatri knee OA patients. The studied G-to-A mutation was found to be positive in 24.8% of controls and 16% of cases, odds ratio (95% confidence interval) being 0.6 (0.19-1.98, P = 0.42). The frequency of AA (D) genotype found around 3% (cases) and 8% (controls) with P value of 0.70. The combined frequency of both homozygous and heterozygous mutation (GA and AA) in the studied population was 28 (27.7%) in controls and 6 (24%) in cases with the odds ratio (OD) ratio of 0.82 (0.29-2.27, P = 0.70). No significant differences were observed at both genotype and allelic level in the distribution of ANKH-4 G-to-A gene polymorphism in studied subjects. CONCLUSION: This study did not show any significant G to A mutation in the studied subjects.

Molecular and clinical insights into protein misfolding and associated amyloidosis.

The misfolding of normally soluble proteins causes their aggregation and deposition in the tissues which disrupts the normal structure and function of the corresponding organs. The proteins with high ß-sheet contents are more prone to form amyloids as they exhibit high propensity of self-aggregation. The self aggregated misfolded proteins act as template for further aggregation that leads to formation of protofilaments and eventually amyloid fibrils. More than 30 different types of proteins are known to be associated with amyloidosis related diseases. Several aspects of the amyloidogenic behavior of proteins remain elusive. The exact reason that causes misfolding of the protein and its association into amyloid fibrils is not known. These misfolded intermediates surpass the over engaged quality control system of the cell which clears the misfolded intermediates. This promotes the self-aggregation, accumulation and deposition of these misfolded species in the form of amyloids in the different parts of the body. The amyloid deposition can be localized as in Alzheimer disease or systemic as reported in most of the amyloidosis. The amyloidosis can be of acquired type or familial. The current review aims at bringing together recent updates and comprehensive information about protein amyloidosis and associated diseases at one place.

Correction to: Oral vitamin A supplementation in very low birth weight neonates: a randomized controlled trial.

The authors regret that Ethical approval section was incorrect in the original publication; the authors have requested that this be noted.

Oral vitamin A supplementation in very low birth weight neonates: a randomized controlled trial.

This randomized double-blind placebo-controlled trial evaluated the effects of early postnatal oral vitamin A supplementation (VAS) in 196 inborn very-low birth weight (VLBW) infants requiring respiratory support at 24 h of age. Eligible infants were randomized to receive aqueous syrup of vitamin A (10,000 IU of retinol/dose; n = 98) or placebo (n = 98) on alternate days for 28 days. Primary outcome variable was composite incidence of all-cause mortality and/or oxygen requirement for 28 days. Secondary outcome variables were safety/tolerability of VAS, serum retinol concentration at recruitment and day 28, duration of oxygen requirement and respiratory support and incidences of complications. On intention-to-treat analysis, composite incidence of all-cause mortality and oxygen requirement for 28 days was significantly lower in vitamin A group (relative risk (95% confidence interval), 0.440 (0.229-0.844); p < 0.05, number needed to benefit, 7). Requirement and duration of oxygen supplementation and non-invasive respiratory support, incidences of late-onset sepsis, patent ductus arteriosus, and duration of hospital stay were also significantly lower in vitamin A group. Serum retinol concentration improved significantly after VAS. No major adverse effect was observed.Conclusions: Early postnatal oral VAS was associated with better composite outcome of all-cause mortality and oxygen requirement without any major adverse effects.Clinical Trial Registration: Clinical Trials Registry of India (CTRI/2017/03/008131). What is Known: • Postnatal intramuscular vitamin A supplementation improves the survival, respiratory outcome and other morbidities in very low birth weight neonates without major adverse effects. • Limited studies on oral vitamin A supplementation did not document substantial benefits. What is New: • Early postnatal alternate-day oral vitamin A supplementation at the dose of 10,000 IU/dose for 28 days improves the composite outcome of death and oxygen requirement in very low birth weight neonates with respiratory distress • No major adverse effects were documented.

Distribution of rheumatological diseases in rural and urban areas: An adapted COPCORD Stage I Phase III survey of Lucknow district in north India.

OBJECTIVES: To study the distribution of various rheumatological diseases in rural and urban areas of Lucknow, India. METHOD: A study using adapted a Community Oriented Program for the Control of Rheumatic Diseases scheme was carried out in a cluster of rural (n = 5118) and urban (n = 5053) communities through a door-to-door survey. Trained community volunteers completed the questionnaires. Patients with musculoskeletal pain (MSK pain) were clinically evaluated by a physician. X-ray examinations and blood investigations were also done. Diagnosis was made according to International Classification of Diseases-9 classification system. RESULTS: Among persons reporting MSK pain in rural areas, high prevalence of osteoarthritis (OA) knee (35%) was observed followed by fibromyalgia (32.1%), backache (28.4%), non-specific pain (NSP) (20.7%) and rheumatoid arthritis (RA) (1.2%). In urban area, OA knee (36.3%) and backache (36.6%) were found highly prevalent, followed by fibromyalgia (11.1%), NSP (10.9%) and neck pain (7.4%). In urban areas among MSK pain patients, prevalence of RA was only 1.6%. Age-adjusted analysis among urban people showed backache complaints begin early (>20 years) than rural people. Significantly higher numbers of Knee OA complaints emerged among urban people than rural in the age group 21-60 years. Projected population prevalence of knee OA was 44.9 and 106.07/1000 in rural and urban areas, respectively. Further projected population prevalences of fibromyalgia, backache, RA and NSP in rural and urban areas are 41.2 and 32.4, 36.5 and 106.6, 1.56 and 4.74, 26.0 and 32.0 per 1000, respectively. CONCLUSION: OA knee, fibromyalgia, backache and NSP are predominant health problems of both areas. Female preponderance was observed in all rheumatological diseases in both the areas.

Development of graft copolymer of carboxymethylcellulose and N-vinylcaprolactam towards strong antioxidant and antibacterial polymeric materials.

The present paper reports graft copolymerization of N-vinylcaprolactam (NVCL) onto carboxymethylcellulose (CMC) using tert-butyl hydroperoxide (TBHP) initiator in N2 atmosphere. The grafting was found to be highest when concentrations of CMC, NVCL and TBHP were 6.25×10-2gdm-3, 10×10-3moldm-3 and 20×10-5moldm-3 respectively. The graft copolymer (CMC-g-PNVCL-1) was characterized by FTIR, 1HNMR, SEM, AFM, XRD and TGA analysis. The antioxidant activity of the graft copolymer was found to be higher (3.81%) than CMC and slightly less (5.47%) than the standard one (butylated hydroxytoluene, BHT). The hydroxyl radical scavenging activity of graft copolymer was found to be slightly less (13.69%) than CMC and more (44.20%) than the BHT. The hydrogen peroxide scavenging activity of graft copolymer was observed to be less (20.42%) than CMC and 53.34% less than BHT. The superoxide scavenging activity of graft copolymer was greater than the both. Compared to CMC the graft copolymer has shown greater antibacterial activity against S. aureus, Proteus vulgaris and S. typhi bacteria and less against Klebsiellapneumonia and Salmonella typhimurium.

Oral Methotrexate in split dose weekly versus oral or parenteral Methotrexate once weekly in Rheumatoid Arthritis: a short-term study.

OBJECTIVE: To investigate whether methotrexate (MTX) administered orally to rheumatoid arthritis (RA) patients in split doses at 2-3 days' interval, would result in equal or better efficacy, tolerability and compliance, without increasing toxicity compared to single weekly dose given orally or parenterally. MATERIALS AND METHODS: One hundred and thirty-five patients fulfilling the American College of Rheumatology (ACR) 2010 criteria for RA, on 7.5 mg of MTX weekly orally, with the Simplified Disease Activity Index (SDAI) > 11 were enrolled for a 24-week period. Patients were randomly divided into three groups and were given MTX: Group 1 7.5 mg twice or thrice weekly orally, Group 2 15 mg or 22.5 mg in a single dose weekly orally and Group 3 15 mg or 22.5 mg in a single dose weekly as an intramuscular injection. The primary outcomes were low disease activity (LDA) and mean change in SDAI at week 24, whereas secondary outcomes included remission, adverse events and compliance. RESULTS: At week 24, adherence to treatment was maximum in Group 1, 69% (P = 0.09). In intention-to-treat analysis at 24 weeks, Group 1, 49%, Group 2, 36% and Group 3, 47% achieved LDA (P = 0.4). There was significant difference in mean change in SDAI at week 24 from baseline (P = 0.008) among the groups. Group 3 patients were more uncomfortable with the mode of administration of MTX (P = 0.003). There was no significant difference in adverse events. CONCLUSION: Oral split doses of MTX are better than an oral single dose and similar to parenteral MTX in terms of efficacy.

Performances of Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) appear to be better than the gold standard Disease Assessment Score (DAS-28-CRP) to assess rheumatoid arthritis patients.

BACKGROUND/PURPOSE: To compare the performance of Disease Assessment Score of 28 joints - C-reactive protein (DAS-28-CRP), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) composite measures to assess status of patients with rheumatoid arthritis (RA) on methotrexate, versus DAS-28 CRP as the gold standard. METHODS: One hundred and thirty-five patients with RA as per the 2010 American College of Rheumatology/European League Against Rheumatism criteria were included in the prospective study. The disease activity was assessed at baseline and at every 6 weeks for 24 weeks, by DAS-28-CRP, CDAI and SDAI. Patients were divided into groups of remission, low, moderate and high activity on the basis of predefined cut-offs for DAS-28-CRP, CDAI and SDAI. A Spearman correlation between composite measures and inter-group comparison of the measures was performed. RESULTS: There was an excellent positive correlation between DAS-28-CRP and CDAI (linear weighted κ baseline - 0.545), DAS-28 CRP and SDAI (linear weighted κ - 0.689) at baseline. There was moderate agreement between DAS-28-CRP and CDAI (linear weighted κ final visit - 0.458) at final visit. There was moderate correlation between SDAI and DAS-28-CRP at final visit (linear weighted κ - 0.470). However, correlation between CDAI versus SDAI remained excellent at baseline and final visit. Patients in remission as per DAS-28-CRP had significantly more residual disease activity compared to SDAI and CDAI remission criteria. CONCLUSION: The study shows an excellent strong positive correlation between DAS-28-CRP, CDAI and SDAI at initial evaluation but not at final visit. SDAI- and CDAI-based remission criteria seem to be better than DAS-28-CRP-based remission criteria.