A Comparative Evaluation of Surface and Elemental Changes in Stainless Steel and Titanium Orthodontic Mini-screw Implants: A Multi-arm Randomized Control Trial.

OBJECTIVE: The present study aimed to compare and quantify the surface changes seen in two most commonly used orthodontic miniscrew implants (MSI) materials; titanium and stainless steel after their clinical use. METHODS: 40 MSIs (20 titanium and 20 stainless steel) were retrieved from the maxillary arch of 20 subjects (13 females and 7 males) in the age group of 18 - 27 years (mean age=22.4 ± 3.83 years) after their intended use. 40 (20 titanium and 20 stainless steel) asreceived MSIs were used as control. All the MSIs were analyzed under a Scanning Electron Microscope (SEM) for the characterization of their morphological condition (blunting of tip, surface defects and corrosion). Furthermore, Energy Dispersive X-ray (EDX) microanalysis was carried out to study the changes in surface characterization. RESULTS: When imaged using SEM, as-received Titanium and Stainless Steel MSIs demonstrated a relatively smooth surface with no surface defects. However, the retrieved titanium and stainless-steel implants showed increased surface defects (both corrosion and cracks) with the difference being statistically significant. The retrieved Titanium MSIs (115.31±24.38µm) showed 4 times more blunting compared to the retrieved Stainless-steel MSIs (29.74±8.56 µm), with the latter showing 2-3 times more surface corrosion. CONCLUSION: Clinical usage had pronounced effects on both Titanium and Stainless steel MSI alloys in terms of changes in the surface characteristics. While stainless steel MSIs are more susceptible to surface corrosion, Titanium MSIs exhibit greater alterations in the form of tipblunting and cracks in screw threads.

New discoveries in progressive myoclonus epilepsies: a clinical outlook.

INTRODUCTION: Progressive myoclonus epilepsies (PMEs) constitute a rare and heterogeneous group of genetic disorders with a distinctive triad of myoclonus, seizures, and progressive neurological deterioration. PMEs, even though rare, are arguably the severest form of epilepsies accounting for <1% of all epilepsies with age at onset varying from infancy to adulthood, depending on the disease. A majority are inherited as autosomal recessive traits, however rare types following autosomal dominant and mitochondrial inheritance are also present. Areas covered: This review discusses the genetics, molecular pathogenesis, and diagnosis of six major forms of PMEs, the current pharmacological interventions under practice and alternative treatment strategies. It also provides an update on the contemporary attempts, such as gene therapy, for etiological treatment of PMEs. Finally, it comments on the autophagy and lysosomal dysfunction, which has emerged as a unifying mechanism underlying the neurodegeneration in PMEs. Expert commentary: Despite the tremendous progress made in identifying the defective genes and dissecting their functional pathways, no etiological treatment is currently available. Thus, an integrated approach to personalized medicine with new drugs, gene therapy, and enzyme replacement therapy hold the promise in pursuit of neurotherapeutic treatment of PMEs.

Abundance matters: role of albumin in diabetes, a proteomics perspective.

INTRODUCTION: Human serum albumin (HSA) is a multifaceted protein with vital physiological functions. It is the most abundant plasma protein with inherent capability to bind to diverse ligands, and thus susceptible to various post-translational modifications (PTMs) which alter its structure and functions. One such PTM is glycation, a non-enzymatic reaction between reducing sugar and protein leading to formation of heterogeneous advanced glycation end products (AGEs). Glycated albumin (GA) concentration increases significantly in diabetes and is implicated in development of secondary complications. Areas covered: In this review, we discuss in depth, formation of GA and its consequences, approaches used for characterization and quantification of GA, milestones in GA proteomics, clinical relevance of GA as a biomarker, significance of maintaining abundant levels of albumin and future perspectives. Expert commentary: Elevated GA levels are associated with development of insulin resistance as well as secondary complications, in healthy and diabetic individuals respectively. Mass spectrometry (MS) based approaches aid in precise characterization and quantification of GA including early and advanced glycated peptides, which can be useful in prediction of the disease status. Thus GA has evolved to be one of the best candidates in the pursuit of diagnostic markers for prediction of prediabetes and diabetic complications.

Proteomic Insight Reveals Elevated Levels of Albumin in Circulating Immune Complexes in Diabetic Plasma.

A Hyperglycemic condition in diabetes promotes formation of advanced glycation end products, which are known to elicit immune response and form complexes with immunoglobulins called circulating immune complexes. To investigate the involvement of advanced glycation end product (AGE)-modified proteins in the elicitation of an immune response, circulating immune complexes were isolated and proteins associated were identified and characterized. Label-free-based mass spectrometric analysis of circulating immune complexes in clinical plasma of prediabetic, newly diagnosed diabetes, and diabetic microalbuminurea revealed elevated levels of serum albumin in the circulating immune complexes, which were also observed to be AGE modified. Further, to examine the role of glycation, circulating immune complexeswere analyzed in the streptozotocin-induced diabetic mice treated with or without aminoguanidine, a prototype glycation inhibitor. Mass spectrometric analysis of circulating immune complexes showed elevated levels of serum albumin in plasma from diabetic mice over that of control animals. Aminoguanidine-treated diabetic mice displayed decreased AGE modification of plasma albumin, accompanied by a reduced level of albumin in the circulating immune complexes. In addition, elevated levels of proinflammatory cytokines such as IL-1b, IL-2, and TNF-alpha were observed in diabetes, which were reduced with aminoguanidine treatment, suggesting the involvement of glycation in the immune response.

Development of Diagnostic Fragment Ion Library for Glycated Peptides of Human Serum Albumin: Targeted Quantification in Prediabetic, Diabetic, and Microalbuminuria Plasma by Parallel Reaction Monitoring, SWATH, and MSE.

Human serum albumin is one of the most abundant plasma proteins that readily undergoes glycation, thus glycated albumin has been suggested as an additional marker for monitoring glycemic status. Hitherto, only Amadori-modified peptides of albumin were quantified. In this study, we report the construction of fragment ion library for Amadori-modified lysine (AML), N(ε)-(carboxymethyl)lysine (CML)-, and N(ε)-(carboxyethyl)lysine (CEL)-modified peptides of the corresponding synthetically modified albumin using high resolution accurate mass spectrometry (HR/AM). The glycated peptides were manually inspected and validated for their modification. Further, the fragment ion library was used for quantification of glycated peptides of albumin in the context of diabetes. Targeted Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH) analysis in pooled plasma samples of control, prediabetes, diabetes, and microalbuminuria, has led to identification and quantification of 13 glycated peptides comprised of four AML, seven CML, and two CEL modifications, representing nine lysine sites of albumin. Five lysine sites namely K549, K438, K490, K88, and K375, were observed to be highly sensitive for glycation modification as their respective m/z showed maximum fold change and had both AML and CML modifications. Thus, peptides involving these lysine sites could be potential novel markers to assess the degree of glycation in diabetes.

Immune response to chemically modified proteome.

Both enzymatic and nonenzymatic PTMs of proteins involve chemical modifications. Some of these modifications are prerequisite for the normal functioning of cell, while other chemical modifications render the proteins as "neo-self" antigens, which are recognized as "non-self" leading to aberrant cellular and humoral immune responses. However, these modifications could be a secondary effect of autoimmune diseases, as in the case of type I diabetes, hyperglycemia leads to protein glycation. The enigma of chemical modifications and immune response is akin to the "chick-and-egg" paradox. Nevertheless, chemical modifications regulate immune response. In some of the well-known autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, chemically modified proteins act as autoantigens forming immune complexes. In some instances, chemical modifications are also involved in regulating immune response during pathogen infection. Further, the usefulness of proteomic analysis of immune complexes is briefly discussed.

Proteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation.

The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein glycation, as well as presence of hydralazine-glucose conjugate in urine of diabetic mice treated with hydralazine. Hydralazine down regulated the expression of Receptor for Advanced Glycation End products (RAGE), NADPH oxidase (NOX), and super oxide dismutase (SOD). These findings will provide a new dimension for developing intervention strategies for the treatment of glycation associated diseases such as diabetes complications, atherosclerosis, and aging.

KD loop for increasing arch perimeter in cleft and noncleft cases.

One of the many indications for dental arch expansion in treating malocclusion is to achieve arch compatibility, especially in surgical cases with severe Bolton discrepancies or collapsed arches due to congenitally missing anterior teeth. These cases usually require expansion in both the sagittal and transverse plane to achieve normal arch compatibility. Arch compatibility can be achieved by either dentoalveolar or skeletal expansion or both. Orthodontically, dentoalveolar expansion can be achieved by means of expanded arch form, vertical loops, or an added assembly such as a quad helix or Ni-Ti expander from the palatal or lingual aspect of the arch. However, these modalities normally provide expansion along transverse plane. If any expansion along sagittal plane is required, then additional appliances such as TransForce or modifications in the appliance system (eg, a quad helix with extension on anterior teeth) are necessary. Vertical loops do overcome these drawbacks to a certain extent; however, at the expense of generating moments during preactivation, which may lead to tipping of segments adjacent to the loop and precludes its use for larger changes of arch dimension. This article describes a new loop design--the KD loop--that increases the arch perimeter by sagittal and transverse expansion without generating significant moments along vertical plane.

Clinical efficiency of nonconventional elastomeric ligatures in the canine retraction phase of preadjusted edgewise appliance therapy: an in-vivo study.

INTRODUCTION: Various ligation techniques and materials have been shown to affect the frictional resistance and the rate of tooth movement with sliding mechanics for space closure. The aim of this study was to evaluate the clinical efficiency of nonconventional elastomeric ligatures and conventional elastomeric ligatures during the canine retraction phase by comparing the rates of canine retraction. METHODS: The 20 patients (12 female, 8 male) in our sample had individual canine retraction (in the first premolar extraction space) in each quadrant (2 maxillary, 2 mandibular) with nonconventional elastomeric ligatures and conventional elastomeric ligatures on either side of the arch. The amount of canine retraction in each interval of 1 month was determined. The rate of canine retraction was calculated and subjected to statistical calculations. RESULTS: The rates of canine retraction were higher with the nonconventional elastomeric ligatures. However, no statistically significant difference was observed in relation to the maxillary arch. Clinically, in most instances, canine retraction was completed in the same interval in both groups. CONCLUSIONS: No significant difference in the rate of canine retraction was observed between the nonconventional elastomeric ligature and conventional elastomeric ligature groups in the maxillary arch. Clinically, the nonconventional elastomeric ligature group showed no reduction in time required for complete canine retraction in the maxillary and mandibular arches.

Proteomic analysis of glycated proteins from streptozotocin-induced diabetic rat kidney.

Glycation of proteins leading to formation of advanced glycation end products (AGEs) has been considered as one of the important causes of diabetic nephropathy. Therefore, in this study, glycated proteins were detected by anti-AGE antibodies from kidney of streptozotocin-induced diabetic rat showing nephropathic symptoms, by using two dimensional electrophoresis and western blot analysis. These glycated proteins were identified and characterized by using combination of peptide mass finger printing and tandem mass spectrometric approaches. Glycated proteins identified included proteins from metabolic pathways, oxidative stress, cell signaling, and transport. Several of the proteins modified by glycation were involved in glucose metabolism. The extent of glycation was higher in diabetes compared to control, in the glycated proteins that were common to both control and diabetic kidney. Two dimensional electrophoresis proteins profiling of glycated proteins suggest that four of the glycated proteins were significantly up regulated in diabetes.

Assessment of the reliability of root angulations on panoramic radiographs.

AIM: To check the reliability of panoramic radiographs in assessing mesiodistal angulations while considering the true long axes of teeth in relation to a horizontal reference archwire. METHOD: A clear anatomical typodont with removable teeth was used with 0.8-mm chromium steel balls glued over the incisal/occlusal and apical/furcal portions of teeth to serve as reference markers for representing true long axes of teeth on radiographs and photographs. A photograph of each tooth was taken with a particular technique to serve as a medium through which to measure true mesiodistal angulations of teeth. RESULTS: Only overall maxillary teeth angulations significantly correlated to true mesiodistal angulations. Radiographic relationship of the long axes of adjacent teeth (convergence or divergence) in the mandibular as well as the maxillary arch did not show any significant correlation to true degree of convergence or divergence and displayed a tendency to accentuate the maxillary canine to premolar divergence and mandibular lateral incisor to canine convergence. CONCLUSION: Panoramic radiographs provide a poor representation of the mesiodistal angulations of teeth and require cautious use with clinical judgment and adjunctive procedures to ascertain root angulations.

Double impact: intrusion of two mandibular molars using an SAS--a case report.

The size of the envelope of tooth movements using fixed mechanotherapy has been increased with the use of temporary anchorage devices (TADs). Orthodontic mini-implants, a form of TADs, have been successfully used for achieving a variety of tooth movements, such as bodily retraction, extrusion, protraction, and even intrusion of maxillary molars. However, the use of orthodontic mini-implants for intruding mandibular molars is questionable due to anatomical constraints. Skeletal anchorage systems (SASs), another form of TADs, overcome these limitations to give promising results for mandibular molar intrusion. The following case report shows the use of unilateral SAS for intruding two mandibular molars and extruding a maxillary molar of the same side to establish a stable occlusal plane. The amount of intrusion achieved in relation to mandibular molars was evaluated by comparing panoramic images. The mandibular left first and second molars were intruded by approximately 1.6 and 2.5 mm, respectively, in relation to the occlusal plane.