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If a crystal undergoes mechanical stress, then an electrical potential is developed across its sides; this phenomenon is called piezoelectricity, or the piezoelectric effect. Piezoelectric materials include quartz, zinc oxide (ZnO), lead zirconate titanate (PZT4), and Rochelle salt. There are numerous uses for piezoelectricity in signal and electrical transducers. In this work, transitional and creep stresses are evaluated in a thin disc made up of piezoelectric transversely isotropic solids subjected to rotation. The mathematical expressions of stress components are computed for the rotating disc by using Seth’s transition theory considering the rotation effect in circular disc. The electric displacement relations and various stress components are computed using Hooke’s Law. A non-homogeneous differential equation is obtained by using mathematical relations and the equilibrium equation. The theoretical solution of the differential equation is obtained under specified boundary conditions. Creep stresses are studied for the considered material. The obtained results are shown graphically, analyzed numerically, and concluded with a discussion of the results for transversely isotropic piezoelectric materials such as BaTiO3 and PZT-4, among others. On the basis of all the numerical discussions and graphs, it is concluded that discs composed of transversely isotropic piezoelectric (PZT4 and BaTiO3) materials are more stable than discs composed of transversely isotropic (magnesium and beryl).

The present chapter developed a preservation-based inventory model under the condition of carbon emissions and the effect of learning on perishable goods. Carbon emissions exit from many sources and affect the greening level of the environment. It is considered that carbon emissions exit due to electricity and also for many more reasons. Finally, total inventory cost will be minimized concerning the cycle length. For the validation of this model, a numerical example has been given and briefly justified with the help of sensitivity analysis. The effect of inventory parameters has shown separately in the sensitivity section.

The partial differential equation (PDE)-based models are widely used to remove additive Gaussian white noise and preserve edges, and one of the most widely used methods is the total variation denoising algorithm. Total variation (TV) denoising algorithm-based time-dependent models have seen considerable success in the field of image-denoising and edge detection. TV denoising algorithm is based on that signals with spurious detail have a high total variation and reduction of unwanted signals to achieve noise-free images. It is a constrained optimization-type algorithm. The Lagrange multiplier and gradient descent method are used to solve the TV algorithm to reach the PDE-based time dependent model. To eliminate additive noise and preserve edges, we investigate a class of weighted time-dependent model in this study. The proposed method is investigated in a well-balanced flow form that extends the time-dependent model with an adaptive fidelity element. Adaptive function is fusing into the regularization term of the classical time-dependent model which successfully enhances the intensity of the regularizer function. We maintain the ability of the time-dependent model without any oscillation effects. Furthermore, we want to prove the viscosity solution of our weighted and well balanced time-dependent model, demonstrating its existence and uniqueness. The finite difference method is applied to discretize the nonlinear time-dependent models. The numerical results are expressed as a statistic known as the peak signal-to-noise ratio (PSNR) and structural similarity index metric (SSIM). Numerical experiments demonstrate that the proposed model yields good performance compared with the previous time-dependent model.

This work investigates piecewise Vand der Pol oscillator under the arbitrary order, piecewise derivatives, and power nonlinearities to present a novel idea of piecewise systems using the classical-power-law randomness and classical Mittag–Leffler-law-randomness. We are able to study the dynamics of piecewise Van der Pol oscillators because the oscillator is one of the prototype models of the systems. It has become famous for examining the dynamics of the systems. To obtain the approximate solution for the aforementioned system, the famous Adams–Bashforth method is applied. The algorithm for obtaining numerical solutions is presented as well as the obtained results were presented graphically along with their different behavior. This oscillator is successfully applied to the model, a diversity of physical processes like nonlinear electronic circuits. Despite the simplicity of this oscillator, the behavior of the models is extremely prosperous and research is still ongoing.

Objective The paradigm of surgical therapy for spinal disease especially for lumbar disc herniation (LDH) has gradually shifted from the traditional open surgeries to minimal invasive spinal surgeries. Endoscopic discectomy has been performed widely using various devices and techniques. In this study we present our experience of endoscopic discectomy using a unique device with separate side-viewing channel. Methods Twenty-six patients with LDH treated between March 2015 and April 2018 using the unique conical working tube with separate side-viewing endoscopic channel have been retrospectively analyzed. Their preoperative and postoperative Oswestry Disability Index (ODI) and Macnab scores were used to evaluate the outcome with a mean follow-up of 37.04 months. Results There were 18 males and 8 females with age ranging from 19 to 72 years (mean, 38.4 years). The follow-up ranged from 25 to 60 months with mean of 37.04 months. The mean preoperative ODI score was 72.4, which decreased to a mean of 7.6 and the outcome evaluated by Macnab criteria was 65.3% excellent, 19.2% good, 11.5% fair, and 3.8% poor. One patient underwent second surgery. None of the patients had to change their occupation postoperatively. Complications that occurred were dural tear in one patient and transient foot paresis in one, which improved spontaneously. Conclusion Endoscopic discectomy using conical working tube is a safe and effective technique for lumbar disc prolapse. The long-term results are comparable to the conventional techniques.

In this article, we formulate the concept of generalize bonvexity/pseudobonvexity functions. We formulate duality results for second-order fractional symmetric dual programs of G-Wolfe-type model. In the next section, we explain the duality theorems under generalize bonvexity/pseudobonvexity assumptions. We identify a function lying exclusively in the class of generalize pseudobonvex and not in class of generalize bonvex functions. Our results are more generalized several known results in the literature.

The Wolfe-type model over arbitrary cones is a new sort of model that we introduce in this article. We defend duality theorems under more generalized higher-order assumptions in the section after this. We identify a function that only belongs to the class of generalize higher order pseudoinvex functions, not the class of generalize higher order invex functions. In the last section, we added a conclusion for future prosecutions for the researchers. Additionally, compared to earlier results in the literature, all of the results in this research are more broadly applicable.

Introduction: The aim of this study was to investigate the efficacy and safety of using a neo-adjuvant concomitant chemoradiation therapy to treat potentially resectable adenocarcinoma of the gastroesophageal junction & proximal stomach. Methods: Thirty-nine patients having potentially resectable adenocarcinoma at the gastroesophageal junction & proximal stomach were recruited in this study to investigate the efficacy and safety of using a neoadjuvant concomitant chemoradiotherapy followed by surgery. Radiation Therapy was performed with a total of 41.4 Gy delivered in 23 sessions (05 fractions/week) along with weekly concurrent chemotherapy (Paclitaxel 50mg/m2 & Carboplatin AUC-2). Results: Of 39 patients, 38 completed the neoadjuvant concurrent chemoradiation without any severe grade 3-4 toxicities. After completion of the therapy, 89.7% had a significant endoscopic response. Thirty-five patients underwent surgery and all patients had an R0-resection. The pathological complete response rate was 14.7%. The maximum & minimum follow ups who completed the treatment protocol (neoadjuvant chemoradiation followed by surgery) reported was 16 & 02 months respectively. 02 patients recurred locally and 01 patient relapsed in bones. Overall, one year survival was 91.3%. Conclusion: The integration of neoadjuvant concurrent chemoradiation is highly effective over preoperative chemotherapy or surgery alone with acceptable toxicity rates.

Introduction Traumatic brain injury (TBI) is a global health issue, accounting for a significant number of adult and pediatric deaths and morbidity. Computed tomography (CT) is an important diagnostic modality for TBI. The primary goal of this study was to determine if there were any significant radiological differences in CT brain findings between adult and pediatric populations. Materials and Methods Data of individual patients were collected from admission to discharge/death, which included various parameters in terms of demographics, mechanism of injury, and patient outcome which were later analyzed. A total of 1,150 TBI patients were enrolled in the study. Results The most common mode of injury in adults is road traffic accident (RTA) followed by fall from height (FFH), while in pediatrics it is vice versa. Findings of basal cisterns on CT brain were found to be statistically significant in both groups; 65% adults and 71% pediatrics had only one abnormal CT finding. Most common combination CT finding in adults was acute subdural hematoma (ASDH) and basal cistern abnormality, while in pediatrics it was traumatic subarachnoid hemorrhage (SAH) and contusion. Rotterdam score (based on CT brain findings) was significantly lower for pediatric age group compared with adults. It was 2.2 ± 0.85 for adults and 1.99 ± 0.74 for pediatrics, which was statistically significant (p < 0.001). Conclusions The Rotterdam score has immense predictive power for prognostication of mortality status. Pediatric age group has better prognosis in terms of survival as compared with adults, thus justifying the role of Rotterdam CT score for mortality risk stratification in providing clinical care.

The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released free radicals. The primary goal of DM treatment is to reduce the risk of micro- and macro-complications. In this study, we looked at the efficacy of aminoguanidine (AG) to prevent the production of early glycation products in alloxan-diabetic rabbits. Type1 DM was induced in rabbits by a single intravenous injection of alloxan (90 mg/kg body weight). Another group of rabbits was pre-treated with AG (100 mg/kg body weight) prior to alloxan injection; this was followed by weekly treatment with 100 mg/kg of AG for eight weeks. Glucose, insulin, and early glycation products (HbA1C and fructosamine) were measured in control, diabetic and AG treated diabetic rabbits. The effects of hyperglycemia on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (rGSH), nitric oxide, lipid peroxides, and protein carbonyl were investigated. Alloxan-diabetic rabbits had lower levels of SOD, CAT, Gpx, and rGSH than control rabbits. Nitric oxide levels were considerably greater. AG administration restored the activities of SOD, CAT, Gpx enzymes up to 70–80% and ameliorated the nitric oxide production. HbA1c and fructosamine levels were considerably lower in AG-treated diabetic rabbits. The observed control of hyperglycemia and amadori adducts in alloxan-diabetic rabbits by AG may be attributed to decrease of stress and restoration of antioxidant defenses.

Tuberculosis of spine, known as Pott’s spine, is a significant health risk. Misdiagnosis or delayed diagnosis with lack of timely interventions lead to serious neurological complications and is associated with morbidity and mortality. We present a case of Pott’s spine who developed tubercular meningitis with decreased vision due to primary optic atrophy, to highlight the significance of thorough clinical and neuroradiological workup with instillation of prompt antitubercular therapy in patients of central nervous system tuberculosis (CNS TB). This association of Pott’s spine with decreased vision secondary to primary optic atrophy due to tubercular involvement of the second cranial nerve is very rare. Here, associated risk factors, varied clinical presentations, complications, and treatment of CNS TB are reviewed.

Background: Parathyroidectomy has been traditionally performed through bilateral neck exploration (BNE). However, with the use of intraoperative parathyroid hormone (IOPTH) assay along with preoperative localization studies, focused parathyroidectomy can be performed with good surgical success rate, multiglandular disease can be predicted, and hence recurrence and surgical failure can be prevented. Furthermore, it predicts eucalcemia in the postoperative period. The aim of this study was to evaluate the usefulness of IOPTH assay in guiding adequate parathyroidectomy in patients of primary hyperparathyroidism. Materials and Methods: Between year 2015 and 2017, 45 patients of primary hyperparathyroidism underwent parathyroidectomy with IOPTH assay employed as an intraoperative tool to guide the surgical procedure. Blood samples were collected: (1) at preincision time, (2) preexcision of gland, (3) 5-min postexcision of gland, and (4) 10-min postexcision of gland. On the basis of the Irvin criterion, an intraoperative PTH drop >50% from the highest either preincision or preexcision level after parathyroid excision was considered a surgical success. Otherwise, BNE was performed and search for other parathyroid glands done. Results: Ten-min postexcision PTH levels dropped >50% in 34 (75.6%) patients. True positive among them were 31 (68.8%), true negative 8 (17.7%), false positive 3 (6.6%), and false negative 3 (6.6%). We performed focused exploration at the outset in 40 (88.9%) patients and bilateral exploration for five patients as guided by preoperative localizing studies. Hence, IOPTH was helpful in guiding further exploration in 8 (17.7%) patients and prevented further exploration in 32 (71.1%) patients and also was able to predict eucalcemia in 97.7% patients at 6 months. Thus, IOPTH was able to obviate or to ask for additional procedure in 88.8% of patients. However, in three (6.6%) patients, IOPTH would guide unnecessary exploration and in equally, that is, three (6.6%) patients may require reoperation for unidentified parathyroids. Conclusion: IOPTH in adjunct with other localizing studies is very helpful for carrying out successful parathyroidectomy in uniglandular disease and predicting postoperative eucalcemia. However, more importantly, its role is valuable in equivocal imaging, in such cases, it prevents unnecessary exploration or helps in adequate parathyroidectomy.

Histone H2B is an autoantigen that appears in circulation due to altered apoptosis/or insufficient clearance and is likely to be involved in the induction and progression of autoimmune diseases since modified-H2B is immunogenic. Our studies demonstrate that tyrosines of H2B histone spontaneously converts to free and nitrotyrosine bound protein in vivo. Commercially available H2B histone was modified with peroxynitrite in vitro. Modified H2B was found to be more immunogenic than native form in experimental animals. Furthermore, the sera of rabbits were analyzed for the native and modified forms of the H2B histone. The binding specificity of autoantibodies was characterized by competitive enzyme-linked immunosorbent assay (ELISA) and band shift assay. The free 3-nitrotyrosine in systemic lupus erythematosus sera was quantified by high-performance liquid chromatography. Peroxynitrite-modified H2B induced high titre antibodies as compared to native form which were directly proportional to the nitrotyrosine content. Furthermore, the induced antibodies showed specificity towards the immunogen and cross-reacted with tyrosine-nitrated proteins. ELISA showed preferential binding of induced anti-peroxynitrite modified H2B antibodies to modified H2B as compared to native H2B. The present study shows that peroxynitrite modification of self-antigen(s) generates neoepitopes capable of inducing modified-H2B autoantibodies in experimental animals.

Background: Total thyroidectomy (TT) is a commonly performed surgery and postoperative hypocalcemia is a major detriment to early discharge. The aim of this randomized controlled trial was to ascertain the usefulness of routine pre- and post-operative calcium and Vitamin D supplementation in prevention of hypocalcemia after TT. Materials and Methods: Sixty consecutive patients who underwent total or near TT from February 2013 to August 2014 were included in the study. They were randomly divided into two groups - Group 1 received oral calcium (500 mg every 6 h) and Vitamin D (calcitriol 0.25 mcg every 6 h) 7 days before and 7 days after the surgery; and Group 2 did not receive supplementation. Symptoms and signs of hypocalcemia were monitored. Calcium profile was measured pre- and post-operatively at 6, 12, 24, 48, 72 h, and on 30th day. Hypocalcemia after surgery was either symptomatic or laboratory documented. Serum calcium level ≤ 8.5 mg/dl was considered as laboratory hypocalcemia. Results: Twelve patients from Group 2, and 3 patients from Group 1 developed symptomatic hypocalcemia (P < 0.01). Laboratory hypocalcemia within postoperative 24 h was comparable between two groups, but more patients of Group 2 compared to Group 1 developed hypocalcemia at 48 h (6 and 13, respectively; P = 0.04) and at 72 h after surgery (5 and 14, respectively; P = 0.01). Twenty-four hours postoperative serum calcium level was significantly associated with grade of goiter, preoperative calcium, and nature of thyroid disease (benign or malignant). On multiple linear regression analysis, preoperative serum calcium was only independent variable significantly associated with development of 24 h post-TT hypocalcemia. Conclusion: Routine pre- and post-TT calcium and Vitamin D supplementation can significantly reduce postoperative hypocalcemia.

Over consumption of fructose may lead to obesity and dyslipidemia and cause fructosylation-induced alterations in the structure and function of proteins. The aim of this study was to investigate the role of fructosylated-HSA-AGE in the pathogenesis of fatty liver (NAFLD and NASH) by biochemical, immunological and histological studies. Immunogenicity of fructosylated-HSA-AGE was probed by inducing antibodies in rabbits. Fructosylated-HSA-AGE was found to be highly immunogenic. Furthermore, fructosylated-HSA-AGE caused mild fibrosis with steatosis and portal inflammation of hepatocytes in experimental animals. Liver function test and dyslipidemic parameters in immunized animals were also found to be raised. Ultrasonography, which should form part of the assessment of chronically raised transaminases, shows fatty infiltration. Interestingly, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, total cholesterol (TC) and triglyceride (TG) profiles confirms USG images of overweight, obese patients. Thus, present study demonstrates that fructosylated-HSA-AGE is hepatotoxic, immunologically active and may cause dyslipidemia.

Background: Although primary hyperparathyroidism (PHPT) has become an asymptomatic disease in the West, in India, PHPT is still an uncommonly diagnosed, overtly symptomatic disease with skeletal, muscular, and renal manifestations. Aims: To describe the profile and surgical outcome of 78 consecutive PHPT patients over a period of two decades at a single center. Materials and Methods: All patients who underwent evaluation and surgery for PHPT from January 1996 to December 2015 were included. Evaluation included measurement of serum total calcium, inorganic phosphorus, alkaline phosphatase, intact parathyroid hormone, 25-hydroxy Vitamin D, 24 hour urinary calcium and radiological survey. Ultrasonography neck and technetium-99m sestamibi scan were used for preoperative localization. Results: A total of 78 patients were identified during the two decades of whom 29 patients were studied retrospectively and 49 patients prospectively. Mean age of patients was 44.72 ± 12.46, and male:female ratio was 1:6. The most common presenting features were nephrolithiasis and/or nephrocalcinosis (64.10%), bone pain (44.1%), abdominal pain (39%), constipation (26%), and myopathy (14.10%). Fractures were present only in 10.25%, and brown tumors in 6.41% patients. The cure rate in our series was 96.15%. The mean parathyroid gland weight was 2.05 ± 3.03 g. None of the 41 patients in whom long-term follow-up was available, had recurrence of PHPT. Conclusions: The profile of PHPT is changing with older age at presentation, and emergence of renal stone disease and decline in overt skeletal disease as common presentation. The parathyroid weight in our study resembles that reported from developed countries.

Hyperglycaemia triggers increased production of methylglyoxal which can cause gross modification in proteins' structure vis-a-vis function though advanced glycation end products (AGEs). The AGEs may initiate vascular and nonvascular pathologies. In this study, we have examined the biochemical and biophysical changes in human IgG under normal and high glucose after introducing methylglyoxal into the assay mixture. This non-enzymatic reaction mainly engaged lysine residues as indicated by TNBS results. The UV results showed hyperchromicity in modified-IgG samples while fluorescence data supported AGEs formation during the course of reaction. Shift in amide I and amide II band position indicated perturbations in secondary structure. Increase carbonyl content and decrease in sulfhydryl suggests that the modification is accompanied by oxidative stress. All modified-IgG samples showed more thermostability than native IgG; the highest Tm was shown by IgG-high glucose-MGO variant. Results of ANS, Congo red and Thioflavin T dyes clearly suggest increase in hydrophobic patches and aggregation, respectively. SEM and TEM images support aggregates generation in modified-IgG samples.

BACKGROUND:Albumin glycation and subsequent formation of advanced glycation end products (AGEs) correlate with diabetes and associated complications. METHODS:Human Serum Albumin (HSA) was modified with D-glucose for a 40 day period under sterile conditions at 37°C. Modified samples along with native HSA (unmodified) were analyzed for structural modifications by UV and fluorescence, FTIR, Liquid chromatography mass spectrometry (LCMS) and X-ray crystallography. New-Zealand white female rabbits immunized with AGEs, represent auto-antibodies formation as assessed by competitive and direct binding enzyme-linked immunosorbent assay (ELISA). Neo-epitopesagainst In-vitro formed AGEs were characterized in patients with diabetes mellitus type 2 (n = 50), type 1 (n = 50), gestational diabetes (n = 50) and type 2 with chronic kidney disease (CKD) with eGFR level 60-89 mL/min (n = 50) from serum direct binding ELISA. RESULTS:Glycated-HSA showed amarked increase in hyperchromicity of 65.82%,71.98%, 73.62% and 76.63% at λ280 nm along with anincreasein fluorescence intensity of 65.82%, 71.98%, 73.62% and 76.63% in glycated-HSA compared to native. FTIR results showed theshifting of Amide I peak from 1656 cm_1 to 1659 cm_1 and Amide II peak from 1554 cm_1 to 1564 cm_1 in glycated-HSA, with anew peak appearance of carbonyl group at 1737 cm-1. LCMS chromatogram of glycated-HSA showed thepresence of carboxymethyl lysine (CML) at 279.1 m/z. Immunological analysis showed high antibody titre>1:12,800 in theserum of rabbits immunized with glycated-HSA (modified with 400 mg/dL glucose) and inhibition of 84.65% at anantigen concentration of 20μg/mL. Maximum serum auto-antibody titre was found in T2DM (0.517±0.086), T1DM (0.108±0.092), GDM (0.611±0.041) and T2DM+CKD (0.096±0.25) patients immunized with glycated-HSA (modified with 400 mg/dL glucose). CONCLUSIONS:Non-enzymatic glycosylation of HSA manifests immunological complications in diabetes mellitus due to change in its structure that enhances neo-epitopes generation.

Glycoxidation plays a crucial role in diabetes and its associated complications. Among the glycoxidation agents, methylglyoxal (MG) is known to have very highglycationpotential witha concomitant generation of reactive oxygen species (ROS) during its synthesis and degradation. The presentstudy probes the MG and ROSinduced structural damage to immunoglobulin G (IgG) and alterations in its immunogenicity in diabetes type 2 patients (T2DM). Human IgG was first glycated with MG followed by hydroxyl radical (OH•) modification. Glycoxidation mediated effects on IgG were evaluated by various physicochemical techniques likeultraviolet (UV) and fluorescence spectroscopy, 8-anilinonaphthalene-1-sulfonic acid (ANS) binding studies, carbonyl andfree sulfhydryl groups assay, matrix assisted laser desorption ionization mass spectrometry-time of flight (MALDI-TOF), red blood cell (RBC) haemolysis assay, Congored (CR) staining analysis and scanning electron microscopy (SEM). The results revealed hyperchromicityin UV, advanced glycation end product (AGE)specific and ANS fluorescence, quenching in tyrosine and tryptophan fluorescence intensity,enhanced carbonyl content,reduction in free sulfhydryl groups,pronounced shift in m/z value of IgGand decrease in antioxidant activity in RBC induced haemolysis assayupon glycoxidation. SEM and CRstaining assay showed highly altered surface morphology in glycoxidised sample as compared to the native. Enzyme linked immunosorbent assay (ELISA) and band shift assay were performed to assess the changes in immunogenicity of IgG upon glyoxidation and its role in T2DM. The serum antibodies derived from T2DM patients demonstrated strong affinity towards OH• treated MG glycatedIgG (OH•-MG-IgG) when compared to native IgG (N-IgG) or IgGs treated with MG alone (MG-IgG) or OH• alone (OH•-IgG). This study shows the cumulating effect of OH• on the glycation potential of MG. The results point towards the modification of IgG in diabetes patients under the effect of glycoxidative stress, leading to the generation of neo-epitopes on theIgG molecule and rendering it immunogenic.

Hyperglycaemia induced non enzymatic glycation is accelerated in diabetic patients and aggressively involved in diabetes progression. Human serum albumin (HSA) is the most abundant protein in blood circulation. In hyperglycaemia, it undergoes fast glycation and results in the impairment of structure. Our previous study has demonstrated structural alterations in Amadori-albumin modified with different glucose concentrations from physiological to pathophysiological range. Here, we focused on immunological characterization of Amadori-albumin. Immunogenicity of Amadori-albumin was analysed by direct binding and competitive ELISA. Amadori-albumin was found to be highly immunogenic (expect albumin modified with 5mM) and induced high titre antibodies depending upon the extent of modification. Very high titre antibodies were obtained with albumin modified with 75mM glucose as compared to native albumin. Anti-Amadori-albumin-IgG from rabbit sera exhibited increased recognition of Amadori-albumin than native albumin in competitive immunoassay. Alteration induced in albumin after glucosylation has made it highly immunogenic. Induced antibodies were quite specific for respective immunogens but showed cross-reaction with other Amadori/native proteins. It suggests that glucosylation has generated highly immunogenic epitopes on albumin. Formation of high molecular weight immune complex with retarded mobility further supports specificity of anti-Amadori-albumin-IgG towards Amadori-albumin. It may be concluded that due to early glycation, an array of modification occurred in HSA structure. Such gross structural changes might favour polymerization of most of the native epitopes into potent immunogenic neo-epitopes, but some original epitopes were still active and has contributed in the immunogenicity. It could be concluded that induction of anti-Amadori-albumin antibodies may be due to protection of glucose modified albumin from protiolytic breakdown. We assumed that this type of protein modifications might occur in diabetic patients in hyperglycaemic conditions that may be recognised as foreign molecules and can induce autoantibodies. Increased level of anti-Amadori-albumin autoantibodies may be used as a biomarker in disease diagnosis and its progression.

Aims: Non-enzymatic glycation of DNA both in vivo and in vitro results in generation of free radicals, known as glycoxidation. Glycoxidation leads to structural perturbation of DNA resulting in generation of neo-antigenic epitopes having implication in autoimmune disorders like diabetes mellitus. In this study human placental DNA was glycated with methylglyoxal (MG) and lysine (Lys) in the presence of Cu2+ and its auto-antibody binding was probed in Type 1 diabetes patients. Methods: Glycation was carried out by incubating DNA with MG, Lys and Cu2+ for 24 h at 37 °C. Carboxyethyl deoxyguanosine (CEdG) formed in glycation reaction was studied by LC-MS and the pathway for Amadori formation was studied by ESI-MS techniques. Furthermore, binding characteristics of auto-antibodies in diabetes patients were assessed by direct binding, competitive ELISA and band shift assay. Results: DNA glycation with MG, Lys and Cu2+ results in the formation of CEdG (marker of DNA glycation) which was confirmed by LC-MS. The intermediate stages of glycation were confirmed by ESI-MS technique. Serum from diabetes patients exhibited enhanced binding and specificity for glycated DNA as compared to native form. Conclusions: Glycation of DNA has resulted in structural perturbation causing generation of neo-antigenic epitopes thus recognizing auto-antibodies in diabetes.

Increased oxidative stress under hyperglycemic conditions, through the interaction of AGEs with RAGE receptors and via activation of interleukin mediated transcription signalling, has been reported in cancer. Proteins modifications are being explored for their roles in the development and progression of cancer and autoantibody response against them is gaining interest as a probe for early detection of the disease. This study has analysed the changes in histone H1 upon modification by methylglyoxal (MG) and its implications in auto-immunopathogenesis of cancer. Modified histone showed modifications in the aromatic residues, changed tyrosine microenvironment, intermolecular cross linking and generation of AGEs. It showed masking of hydrophobic patches and a hypsochromic shift in the in ANS specific fluorescence. MG aggressively oxidized histone H1 leading to the accumulation of reactive carbonyls. Far UV CD measurements showed di-carbonyl induced enhancement of the alpha structure and the induction of beta sheet conformation; and thermal denaturation (Tm) studies confirmed the thermal stability of the modified histone. FTIR analysis showed amide I band shift, generation of a carboxyethyl group and N-Cα vibrations in the modified histone. LCMS analysis confirmed the formation of Nε-(carboxyethyl)lysine and electron microscopic studies revealed the amorphous aggregate formation. The modified histone showed altered cooperative binding with DNA. Modified H1 induced high titre antibodies in rabbits and the IgG isolated form sera of rabbits immunized with modified H1 exhibited specific binding with its immunogen in Western Blot analysis. IgG isolated from the sera of patients with lung cancer, prostate cancer, breast cancer and cancer of head and neck region showed better recognition for neo-epitopes on the modified histone, reflecting the presence of circulating autoantibodies in cancer. Since reports suggest a link between AGE-RAGE axis and carcinogenesis, glycoxidation of histone H1 and its immunogenicity paves ways for understanding role of glycoxidatively damaged nuclear proteins in cancer.

Advanced glycation end-products (AGEs) are heterogeneous group of compounds, known to be implicated in diabetic complications. One of the consequences of the Maillard reaction is attributed to the production of reactive intermediate products such as α-oxoaldehydes. 3-deoxyglucosone (3-DG), an α-oxoaldehyde has been found to be involved in accelerating vascular damage during diabetes. In the present study, calf thymus histone H3 was treated with 3-deoxyglucosone to investigate the generation of AGEs (Nε-carboxymethyllysine, pentosidine), by examining the degree of side chain modifications and formation of different intermediates and employing various physicochemical techniques. The results clearly indicate the formation of AGEs and structural changes upon glycation of H3 by 3-deoxyglucosone, which may hamper the normal functioning of H3 histone, that may compromise the veracity of chromatin structures and function in secondary complications of diabetes.

Advanced glycation end products (AGEs) culminate from the non-enzymatic reaction between a free carbonyl group of a reducing sugar and free amino group of proteins. 3-deoxyglucosone (3-DG) is one of the dicarbonyl species that rapidly forms several protein-AGE complexes that are believed to be involved in the pathogenesis of several diseases, particularly diabetic complications. In this study, the generation of AGEs (Nε-carboxymethyl lysine and pentosidine) by 3-DG in H1 histone protein was characterized by evaluating extent of side chain modification (lysine and arginine) and formation of Amadori products as well as carbonyl contents using several physicochemical techniques. Results strongly suggested that 3-DG is a potent glycating agent that forms various intermediates and AGEs during glycation reactions and affects the secondary structure of the H1 protein. Structural changes and AGE formation may influence the function of H1 histone and compromise chromatin structures in cases of secondary diabetic complications.

BackgroundThe interaction of environmental chemicals and their metabolites with biological macromolecules can result in cytotoxic and genotoxic effects. 4-Aminobiphenyl (4-ABP) and several other related arylamines have been shown to be causally involved in the induction of human urinary bladder cancers. The genotoxic and the carcinogenic effects of 4-ABP are exhibited only when it is metabolically converted to a reactive electrophile, the aryl nitrenium ions, which subsequently binds to DNA and induce lesions. Although several studies have reported the formation of 4-ABP-DNA adducts, no extensive work has been done to investigate the immunogenicity of 4-ABP-modified DNA and its possible involvement in the generation of antibodies in bladder cancer patients.Methodology/principal findingsHuman DNA was modified by N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP), a reactive metabolite of 4-ABP. Structural perturbations in the N-OH-AABP modified DNA were assessed by ultraviolet, fluorescence, and circular dichroic spectroscopy as well as by agarose gel electrophoresis. Genotoxicity of N-OH-AABP modified DNA was ascertained by comet assay. High performance liquid chromatography (HPLC) analysis of native and modified DNA samples confirmed the formation of N-(deoxyguanosine-8-yl)-4-aminobiphenyl (dG-C8-4ABP) in the N-OH-AABP damaged DNA. The experimentally induced antibodies against N-OH-AABP-modified DNA exhibited much better recognition of the DNA isolated from bladder cancer patients as compared to the DNA obtained from healthy individuals in competitive binding ELISA.Conclusions/significanceThis work shows epitope sharing between the DNA isolated from bladder cancer patients and the N-OH-AABP-modified DNA implicating the role of 4-ABP metabolites in the DNA damage and neo-antigenic epitope generation that could lead to the induction of antibodies in bladder cancer patients.

BackgroundThe oxidation of proteins by endogenously generated free radicals causes structural modifications in the molecules that lead to generation of neo-antigenic epitopes that have implications in various autoimmune disorders, including rheumatoid arthritis (RA). Collagen induced arthritis (CIA) in rodents (rats and mice) is an accepted experimental model for RA.Methodology/principal findingsHydroxyl radicals were generated by the Fenton reaction. Collagen type II (CII) was modified by •OH radical (CII-OH) and analysed by ultraviolet-visible (UV-VIS), fluorescence and circular dichroism (CD) spectroscopy. The immunogenicity of native and modified CII was checked in female Lewis rats and specificity of the induced antibodies was ascertained by enzyme linked immunosorbent assay (ELISA). The extent of CIA was evaluated by visual inspection. We also estimated the oxidative and inflammatory markers in the sera of immunized rats. A slight change in the triple helical structure of CII as well as fragmentation was observed after hydroxyl radical modification. The modified CII was found to be highly arthritogenic and immunogenic as compared to the native form. The CII-OH immunized rats exhibited increased oxidative stress and inflammation as compared to the CII immunized rats in the control group.Conclusions/significanceNeo-antigenic epitopes were generated on (•)OH modified CII which rendered it highly immunogenic and arthritogenic as compared to the unmodified form. Since the rodent CIA model shares many features with human RA, these results illuminate the role of free radicals in human RA.

Background A zoonotic, double-stranded DNA virus belonging to the genus Orthopoxvirus, the mpox virus (MPXV) is most common in tropical regions of Central and West Africa. The frequency of monkeypox (mpox) cases, however, has sharply climbed globally since May 2022. Objectives To establish the threat of mpox in terms of the oral lesions caused in sufferers. Materials and methods After a thorough study of the literature identified in the PubMed, Web of Science, and Cochrane library databases using the PRISMA framework, 103 papers were found. Using inclusion and exclusion criteria, we chose research that was relevant for our review before shortlisting 14 papers that conformed to the review's guidelines. Results In the 14 selected studies, it was found that oral lesions were among the first clinical signs of a mpox affliction, with ulcers on the dorsal surface of tongue lips being the most common areas affected. Conclusion The rarely observed oral lesions of mpox infection may help in the diagnosis and management of this condition. It is critical to keep in mind that recognising and detecting oral lesions in mpox patients opens the door to more research and efficient patient management.

Background: A zoonotic, double-stranded DNA virus belonging to the genus Orthopoxvirus, the monkeypox virus is most common in tropical regions of Central and West Africa. The frequency of monkeypox cases, however, has sharply climbed globally since May 2022. Objectives: To establish the threat of monkeypox in terms of the oral lesions caused in sufferers. Materials and methods: After a thorough study of the literature identified in the PubMed, Web of Science, and Cochrane library databases using the PRISMA framework, 103 papers were found. Using inclusion and exclusion criteria, we chose research that was relevant for our review before shortlisting 14 papers that conformed to the review's guidelines. Results: In the 14 selected studies, it was found that oral lesions were among the first clinical signs of a monkeypox affliction, with ulcers on the dorsal surface of tongue lips being the most common areas affected. Conclusion: The rarely observed oral lesions of monkeypox infection may help in the diagnosis and management of this condition. It is critical to keep in mind that recognising and detecting oral lesions in monkeypox patients opens the door to more research and efficient patient management.

Objective: To evaluate the effectiveness of a minimally-invasive corticotomy-assisted treatment of palatally impacted canines (PICs) compared with the traditional method by evaluating treatment time, the velocity of movement, and the associated dentoalveolar changes. Materials and methods: Forty-six patients with palatally or mid-alveolar upper impacted canines were recruited and distributed into two groups: the corticotomy-assisted traction group (CAT group, mean age: 20.39±2.27 years) and the traditional treatment group (TT group, mean age: 20.26±2.17 years). The closed surgical approach was used in both study groups. The velocity of traction movement, traction duration and overall treatment duration were evaluated clinically. In addition, the bone support ratios and the amount of root resorption were assessed on cone-beam computed tomography (CBCT) images. Results: At the end of treatment, significant differences were found between the two groups regarding the velocity of traction movement, traction time, and overall treatment time (Px velocity=1.15±0.35 mm/month; 0.70±0.33 mm/month, P=0.027, respectively). The duration of the active traction and the overall orthodontic treatment in the CAT group were significantly shorter than the TT group by 36% and 29%, respectively. The mean bone support ratios of the aligned canines did not differ significantly between the two groups (88% vs. 89% in the CAT and TT groups, respectively). No significant differences were found between the two groups regarding the mean amount of root resorption on the adjacent laterals ( x resorption = 1.30±1.18 mm; 1.22±1.02 mm, P=0.612, in CAT and TT groups, respectively). Conclusions: The traction movement velocity of the palatally impacted canines can be increased using minimally-invasive corticotomy-assisted orthodontic treatment. The side effects of the acceleration procedure were minimal and almost similar to those of the traditional technique.