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.

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.

Osteoporosis in Postmenopausal Females with Primary Knee Osteoarthritis in a Vitamin D Deficient Population.

AIM AND OBJECTIVE: To find prevalence of osteoporosis (OP) in postmenopausal females with primary knee osteoarthritis (OA) in India, where there is widespread Vitamin D deficiency (VDD). MATERIAL AND METHODS: 75 postmenopausal women (PMW) fulfilling ACR criteria for Knee OA between 40 - 60 years of age, having OA grade 2 or more as per Kellgren Lawrence grade on anterior- posterior radiograph of the right knee were enrolled. 34 PMW of the same age with normal right knee radiograph were taken as controls. Bone mineral density (BMD) of lumber spine (L1- L4), total hip and left forearm was performed using DXA in all patients and controls. The results were expressed in absolute values (g/cm2) and as per WHO criteria - Osteoporosis: T score < -2.5, Osteopenia: T score between -1 and -2.5. Vitamin D Level was done by ELISA. RESULTS: Body mass index (BMI) of patients was significantly higher than controls (p 0.006). There was no difference in BMD between patients and controls at any site. Forty percent patients and 53% controls had osteopenia (p ns), while 34.6% patients and 41.1% controls had osteoporosis at any site (p ns). When this comparison was made at each site there was no difference between patients and controls. CONCLUSION: Prevalence of osteoporosis in PMW with primary knee OA is similar to that in general population.

Problem-focused coping and self-efficacy as correlates of quality of life and severity of fibromyalgia in primary fibromyalgia patients.

OBJECTIVES: Patients with fibromyalgia syndrome (FMS) often experience problems such as poor quality of life (QoL), loss of self-efficacy (SE), inappropriate coping behavior, and chronic widespread pain along with other symptoms. Recent studies have indicated that sense of SE and effective coping strategies (CSs) are the crux on which the management of chronic pain and enrichment of QoL of FMS patients depend. Realizing the importance of this subject for the rehabilitation of the people with FMS, this study aimed at analyzing the correlation between severity of FMS, and QoL, SE, and CSs among the patients of FMS. METHODS: One hundred patients with fibromyalgia (FM) and 100 control subjects were studied. Fibromyalgia Impact Questionnaire-Revised, Quality of Life Scale, Arthritis Self-efficacy Scale, and COPE Scales for CSs were administered to both the groups. RESULTS: Significantly lower SE, poor QoL, and less use of CSs were reported by FM patients (P < 0.01) vis-à-vis healthy people. Problem-focused coping (r = 0.27, P < 0.01) and SE (r = 0.20, P < 0.05) were found to be significantly and positively associated with QoL. Components of Fibromyalgia Impact Questionnaire-Revised, namely, pain, function, and symptoms, were found to be significantly and negatively associated with problem-focused coping (P < 0.05), SE (P < 0.01), and QoL (P < 0.01). CONCLUSIONS: This study confirms that problem-focused CSs and SE are important correlates of QoL and severity of FM in Indian as well as other populations.

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.

Mucosal IgA & IL-1ß in Helicobacter pylori Infection.

Helicobacter pylori infection stimulates strong local inflammatory and specific IgA antibody production. The influence of antibodies on the bacterial colonization is not clear. Here, we have analysed the association between the mucosal IgA level and IL-1ß in various manifestations of the infection seen endoscopically. Antral biopsies of 57 dyspeptic patients were taken for culture, histology and estimation of mucosal levels of anti-H. pylori IgA and IL-1ß. Mean mucosal IgA level was higher in patients with normal mucosa compared to all other groups and lower IgA level was associated with higher bacterial density. IL-1ß was higher in ulcer patients and suspicious malignancy group as compared to normal group and higher level of IL-1ß was associated with higher grades of metaplasia. Present study indicates that local immunity seems to have a protective role against H. pylori infection and higher level of IL-1ß induced by the pathogen may be associated with metaplasia and carcinogenesis.

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.

X-ray knee as a screening tool for osteoporosis.

Cortical thickness (Cor-Th) of tibia varies considerably on X-ray knees. It was hypothesized that Cor-Th can be used for preliminary prediction of BMD. Ninety nine patients underwent a digital X-ray left knee fixed flexion PA view with an external calibration scale attached to X-ray plate and BMD by DXA using GE lunar machine (Madison, Wisconsin.). Cor-Th was measured at 5 selected levels (A,B,C,D, and E) ranging from 5-7 cm below the tibial plateau on its medial aspect. T-scores were recorded for BMD at AP spine, left forearm and left femur. Cor-Th of tibia at each level significantly correlated with each site of BMD measurement namely AP spine, left femur and left forearm. This correlation varied in the range from 0.241 to 0.426. For AP spine, it was maximum at level C (r=0.347, p<0.001) whereas for left femur and forearm sites, it was maximum at level B (r=0.426 &r=0.373 respectively, p<0.001). The correlation of Cor-Th with BMD varied with age. Above 56 years of age, Cor-Th at each level significantly correlated to BMD at each site. Medial tibial cortical thickness, 6 cm (level C) below tibial plateau can be used as preliminary predictor of patients who need a DXA scan.

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.

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.

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.

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.