A technique for correcting the implant analog position in the digitally printed definitive cast.

A straightforward technique is presented for correcting the position of an inaccurately oriented implant analog in a digitally printed definitive cast. The technique enables the operator to reposition the analog accurately in the definitive cast and obviates the need of an additional scanning procedure or printing a new cast. The technique also permits accurate reproduction of the soft tissue contours around the implant.

Parapharyngeal space carcinoma disguised as temporomandibular joint disorder: A clinical report.

Parapharyngeal space neoplasms tend to have a considerable volume by the time of diagnosis because of their deep location in the neck and may have a relatively long progression before becoming symptomatic. Common presenting signs and symptoms of parapharyngeal space neoplasms include swelling in the neck, intraoral mass, dysphagia, dysphonia, heaviness in the ear, otalgia, and rarely, trismus. Some of these signs and symptoms could be mistaken for signs of temporomandibular disorder (TMD). This clinical report presents the incidental discovery of parapharyngeal space carcinoma initially presenting as TMD. A thorough clinical examination of the temporomandibular joints, supported by their magnetic resonance imaging, led to early detection of the neoplasm, thereby improving the patient's post-treatment survival probability.

Cerebrovascular Involvement in Mucormycosis in COVID-19 Pandemic.

BACKGROUND: Many countries have seen an unprecedented rise of cases of coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM). Cerebrovascular involvement in CAM has not been studied so far. We describe clinico-radiological manifestations of cerebrovascular complications observed in CAM. METHODS: In this multicentric retrospective observational study from India, patients with CAM who developed cerebrovascular involvement were studied. Their demographics, risk factors, clinical manifestations, imaging, laboratory profile and outcomes were noted. RESULTS: Out of 49 subjects with cerebrovascular involvement, 71.4% were males while average age was 52.9 years. Ischemic stroke was commonest (91.8%) followed by intracranial haemorrhage (6.1%) and subarachnoid haemorrhage (2%). The incidence of cerebrovascular complications in CAM was found to be 11.8% in one center. Cerebrovascular symptoms appeared a median of 8.3 days from the onset of mucormycosis. Commonest presentation of mucormycosis was rhino-orbito-cerebral syndrome in 98%. Diabetes mellitus was present in 81.7%. Forty percent developed stroke despite being on antiplatelet agent and/or heparin. Amongst subjects with ischemic strokes, location of stroke was unilateral anterior circulation (62.2%); bilateral anterior circulation (17.8%); posterior circulation (11.1%) and combined anterior and posterior circulation (8.9%). Vascular imaging revealed intracranial occlusion in 62.1%; extracranial occlusion in 3.4% and normal vessels in 34.5%. Mortality was 51% during hospital stay. CONCLUSIONS: Cerebrovascular involvement was seen in 11.8% patients of CAM. Angio-invasive nature of the fungus, prothrombotic state created by COVID-19, and diabetes were important causative factors. Subjects with CAM should be screened for involvement of the brain as well as its vessel. Antiplatelet agents/heparin did not seem to provide complete protection from this type of stroke.

An Epidemiological Case Control Multi-centre Trial on Cerebral Venous Sinus Thrombosis in Western Maharashtra, India.

INTRODUCTION: Cerebral Sino-Venous thrombosis (CSVT) is common in India; this country has a heterogeneous population. Genetically and physio-gnomically this population differs in their diet as well as in their environment. Despite these differences CSVT has been described from all quarters of India; a common factor embracing all these patients could be nutrition. OBJECTIVES: An epidemiological, case- control, multi-centre trial was carried out in patients of CSVT. A common factor underlying this could be nutrition which has not been highlighted in several studies. Hence, we studied the nutritional aspects of these patients. METHOD: 63 patients of CSVT and 62 controls enrolled prospectively and followed for a year were investigated with special emphasis on their nutritional status. RESULTS: The triceps skin fold thickness, energy baseline, serum Proteins, Albumin, Hemogram and Platelet counts were lower in patients than in the controls while serum Homocysteine, carbohydrates and fats were higher in patients than in controls. CONCLUSION: The results of this study confirm nutritional deficiencies in patients of CSVT and it begs the question of whether nutrition in any way is causal in CSVT. Larger multi-centric trials will help establishing causality. The study also shows that routine evaluation of thrombophilia factors and immunological tests are not necessary in CSVT.

In vitro fracture resistance of zirconia, glass-fiber, and cast metal posts with different lengths.

AIM: Post-and-core restorations require sufficient length of the post for retention of the prosthesis and root strength. The effect of different lengths of prefabricated zirconia posts (ZPs) on the fracture strength of endodontically treated teeth needs evaluation. Hence, the aim of this study was to evaluate the in vitro fracture resistance of endodontically treated incisors restored with ZP, glass-fiber (GFP), and cast posts (CP) of different lengths. SETTINGS AND DESIGN: Comparative in-vitro study. MATERIALS AND METHODS: Sixty extracted incisors were endodontically treated, tooth preparations were carried out, and the impression of the coronal portion of each prepared tooth was made using polyvinyl siloxane impression material loaded in copper tubes. The coronal portion of each tooth was removed, maintaining a 2 mm ferrule. The teeth were restored with one of the three posts: CPs, GFP, or ZPs, with intraradicular lengths of either 6 or 8 mm (n = 10). The CP and core patterns were fabricated using post space impressions and core buildup and cast using Nickel-Chromium alloy. After composite resin core buildup of GFP and ZPs treated teeth using the previously made copper tube impressions, the teeth were loaded to fracture in an oblique direction in the universal testing machine. STATISTICAL ANALYSIS USED: Data were analyzed using two-way ANOVA and Tukey-Kramer tests (α = 0.05). RESULTS: The highest and lowest values of fracture resistance were reported with ZP8 and GFP6 groups, respectively. There was no significant difference in fracture resistance between the posts of length 6 mm and 8 mm in CP, GFP, and ZP groups. There was no significant difference (P = 0.953) in fracture resistance between CP (284.8 N) and ZP (258.31 N) groups, while the GFP group (160.61 N) had a significantly lower value of fracture resistance than the CP and ZP groups. Two-way ANOVA test for fracture resistance of the post systems and post lengths showed that there was no significant correlation between the post systems and post length on the fracture resistance. There was a greater percentage of favorable fractures in GFP and ZP groups (65% each), than the CP group (20%). CONCLUSION: For the post systems tested, extending the post length does not significantly increase the fracture resistance of the restored teeth. The ZP represents a viable alternative to the cast metal post during the esthetic restoration of endodontically treated anterior teeth.

A stochastic model for post-transcriptional regulation of rare events in gene expression.

Post-transcriptional regulation of gene expression is often a critical component of cellular processes involved in cell-fate decisions. Correspondingly, considerable efforts have focused on modeling post-transcriptional regulation of stochastic gene expression and on quantifying its impact on the mean and variance of protein levels. However, the impact of post-transcriptional regulation on rare events corresponding to large deviations in gene expression is less well understood. Here, we study a simple model involving post-transcriptional control of gene expression and characterize the impact of regulation on large deviations in activity fluctuations. We derive analytical results for the large deviation function for protein production rate and for the corresponding driven process which characterizes system fluctuations conditional on the rare event. Our results suggest that fluctuations in burst size rather than frequency play a dominant role in controlling rare events. The results derived also provide insight into how post-transcriptional regulation can be used to fine-tune the probability of rare fluctuations and to thereby control phenotypic variation in a population of cells.

Constraining the complexity of promoter dynamics using fluctuations in gene expression.

Gene expression is an inherently stochastic process with transcription of mRNAs often occurring in bursts: short periods of activity followed by typically longer periods of inactivity. While a simple model involving switching between two promoter states has been widely used to analyze transcription dynamics, recent experimental observations have provided evidence for more complex kinetic schemes underlying bursting. Specifically, experiments provide evidence for complexity in promoter dynamics during the switch from the transcriptionally inactive to the transcriptionally active state. An open question in the field is: what is the minimal complexity needed to model promoter dynamics and how can we determine this? Here, we show that measurements of mRNA fluctuations can be used to set fundamental bounds on the complexity of promoter dynamics. We study models wherein the switching time distribution from transcriptionally inactive to active states is described by a general waiting-time distribution. Using approaches from renewal theory and queueing theory, we derive analytical expressions which connect the Fano factor of mRNA distributions to the waiting-time distribution for promoter switching between inactive and active states. The results derived lead to bounds on the minimal number of promoter states and thus allow us to derive bounds on the minimal complexity of promoter dynamics based on single-cell measurements of mRNA levels.

Fabrication of custom overdenture attachments using indigenously made parallelometer: A technique.

Various types of attachments have been used during overdenture fabrication; however, no single attachment is perfect for every case. Irrespective of the attachment used, it is important to maintain parallelism between the attachments for ease of insertion and removal, functional efficiency, and durability of the prosthesis. It is challenging to obtain parallelism between attachments when the abutments are divergent, or multiple abutments are engaged. A simplified technique to fabricate cast overdenture attachments using indigenously made parallelometer has been described. This technique eliminates the need of making full-arch impressions and models and surveying the attachments before casting. With this technique, there is a reduction in the duration and cost of treatment, without any compromise in quality of the prosthesis.

Stochastic Modeling of Gene Regulation by Noncoding Small RNAs in the Strong Interaction Limit.

Noncoding small RNAs (sRNAs) are known to play a key role in regulating diverse cellular processes, and their dysregulation is linked to various diseases such as cancer. Such diseases are also marked by phenotypic heterogeneity, which is often driven by the intrinsic stochasticity of gene expression. Correspondingly, there is significant interest in developing quantitative models focusing on the interplay between stochastic gene expression and regulation by sRNAs. We consider the canonical model of regulation of stochastic gene expression by sRNAs, wherein interaction between constitutively expressed sRNAs and mRNAs leads to stoichiometric mutual degradation. The exact solution of this model is analytically intractable given the nonlinear interaction term between sRNAs and mRNAs, and theoretical approaches typically invoke the mean-field approximation. However, mean-field results are inaccurate in the limit of strong interactions and low abundances; thus, alternative theoretical approaches are needed. In this work, we obtain analytical results for the canonical model of regulation of stochastic gene expression by sRNAs in the strong interaction limit. We derive analytical results for the steady-state generating function of the joint distribution of mRNAs and sRNAs in the limit of strong interactions and use the results derived to obtain analytical expressions characterizing the corresponding protein steady-state distribution. The results obtained can serve as building blocks for the analysis of genetic circuits involving sRNAs and provide new insights into the role of sRNAs in regulating stochastic gene expression in the limit of strong interactions.

A modified technique for single-step border molding.

The sectional and the single-step are techniques for border molding. Even though the sectional technique is routinely taught in dental schools in the United States, and is followed by a large number of general dental practitioners, it is not without disadvantages. Common problems associated with the sectional technique include its time-consuming nature and the difficulty in mastering it because of the short manipulation time of the impression compound modeling plastic. Single-step border molding, however, presents advantages; for example, fewer insertions of the tray for border molding are necessary, and development of all borders simultaneously avoids the propagation of error. This article presents a simplified technique for performing single-step border molding using visible light-polymerizing tray material.

Prediction of bacterial small RNAs in the RsmA (CsrA) and ToxT pathways: a machine learning approach.

BACKGROUND: Small RNAs (sRNAs) constitute an important class of post-transcriptional regulators that control critical cellular processes in bacteria. Recent research using high-throughput transcriptomic approaches has led to a dramatic increase in the discovery of bacterial sRNAs. However, it is generally believed that the currently identified sRNAs constitute a limited subset of the bacterial sRNA repertoire. In several cases, sRNAs belonging to a specific class are already known and the challenge is to identify additional sRNAs belonging to the same class. In such cases, machine-learning approaches can be used to predict novel sRNAs in a given class. METHODS: In this work, we develop novel bioinformatics approaches that integrate sequence and structure-based features to train machine-learning models for the discovery of bacterial sRNAs. We show that features derived from recurrent structural motifs in the ensemble of low energy secondary structures can distinguish the RNA classes with high accuracy. RESULTS: We apply this approach to predict new members in two broad classes of bacterial small RNAs: 1) sRNAs that bind to the RNA-binding protein RsmA/CsrA in diverse bacterial species and 2) sRNAs regulated by the master regulator of virulence, ToxT, in Vibrio cholerae. CONCLUSION: The involvement of sRNAs in bacterial adaptation to changing environments is an increasingly recurring theme in current research in microbiology. It is likely that future research, combining experimental and computational approaches, will discover many more examples of sRNAs as components of critical regulatory pathways in bacteria. We have developed a novel approach for prediction of small RNA regulators in important bacterial pathways. This approach can be applied to specific classes of sRNAs for which several members have been identified and the challenge is to identify additional sRNAs.

Stochastic gene expression conditioned on large deviations.

The intrinsic stochasticity of gene expression can give rise to large fluctuations and rare events that drive phenotypic variation in a population of genetically identical cells. Characterizing the fluctuations that give rise to such rare events motivates the analysis of large deviations in stochastic models of gene expression. Recent developments in non-equilibrium statistical mechanics have led to a framework for analyzing Markovian processes conditioned on rare events and for representing such processes by conditioning-free driven Markovian processes. We use this framework, in combination with approaches based on queueing theory, to analyze a general class of stochastic models of gene expression. Modeling gene expression as a Batch Markovian Arrival Process (BMAP), we derive exact analytical results quantifying large deviations of time-integrated random variables such as promoter activity fluctuations. We find that the conditioning-free driven process can also be represented by a BMAP that has the same form as the original process, but with renormalized parameters. The results obtained can be used to quantify the likelihood of large deviations, to characterize system fluctuations conditional on rare events and to identify combinations of model parameters that can give rise to dynamical phase transitions in system dynamics.

Cell motility and ECM proteolysis regulate tumor growth and tumor relapse by altering the fraction of cancer stem cells and their spatial scattering.

Tumors consist of multiple cell sub-populations including cancer stem cells (CSCs), transiently amplifying cells and terminally differentiated cells (TDCs), with the CSC fraction dictating the aggressiveness of the tumor and drug sensitivity. In epithelial cancers, tumor growth is influenced greatly by properties of the extracellular matrix (ECM), with cancer progression associated with an increase in ECM density. However, the extent to which increased ECM confinement induced by an increase in ECM density influences tumor growth and post treatment relapse dynamics remains incompletely understood. In this study, we use a cellular automata-based discrete modeling approach to study the collective influence of ECM density, cell motility and ECM proteolysis on tumor growth, tumor heterogeneity, and tumor relapse after drug treatment. We show that while increased confinement suppresses tumor growth and the spatial scattering of CSCs, this effect can be reversed when cells become more motile and proteolytically active. Our results further suggest that, in addition to the absolute number of CSCs, their spatial positioning also plays an important role in driving tumor growth. In a nutshell, our study suggests that, in confined environments, cell motility and ECM proteolysis are two key factors that regulate tumor growth and tumor relapse dynamics by altering the number and spatial distribution of CSCs.

Transcriptional Bursting in Gene Expression: Analytical Results for General Stochastic Models.

Gene expression in individual cells is highly variable and sporadic, often resulting in the synthesis of mRNAs and proteins in bursts. Such bursting has important consequences for cell-fate decisions in diverse processes ranging from HIV-1 viral infections to stem-cell differentiation. It is generally assumed that bursts are geometrically distributed and that they arrive according to a Poisson process. On the other hand, recent single-cell experiments provide evidence for complex burst arrival processes, highlighting the need for analysis of more general stochastic models. To address this issue, we invoke a mapping between general stochastic models of gene expression and systems studied in queueing theory to derive exact analytical expressions for the moments associated with mRNA/protein steady-state distributions. These results are then used to derive noise signatures, i.e. explicit conditions based entirely on experimentally measurable quantities, that determine if the burst distributions deviate from the geometric distribution or if burst arrival deviates from a Poisson process. For non-Poisson arrivals, we develop approaches for accurate estimation of burst parameters. The proposed approaches can lead to new insights into transcriptional bursting based on measurements of steady-state mRNA/protein distributions.

A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa.

CsrA/RsmA homologs are an extensive family of ribonucleic acid (RNA)-binding proteins that function as global post-transcriptional regulators controlling important cellular processes such as secondary metabolism, motility, biofilm formation and the production and secretion of virulence factors in diverse bacterial species. While direct messenger RNA binding by CsrA/RsmA has been studied in detail for some genes, it is anticipated that there are numerous additional, as yet undiscovered, direct targets that mediate its global regulation. To assist in the discovery of these targets, we propose a sequence-based approach to predict genes directly regulated by these regulators. In this work, we develop a computer code (CSRA_TARGET) implementing this approach, which leads to predictions for several novel targets in Escherichia coli and Pseudomonas aeruginosa. The predicted targets in other bacteria, specifically Salmonella enterica serovar Typhimurium, Pectobacterium carotovorum and Legionella pneumophila, also include global regulators that control virulence in these pathogens, unraveling intricate indirect regulatory roles for CsrA/RsmA. We have experimentally validated four predicted RsmA targets in P. aeruginosa. The sequence-based approach developed in this work can thus lead to several testable predictions for direct targets of CsrA homologs, thereby complementing and accelerating efforts to unravel global regulation by this important family of proteins.

Interdisciplinary approach to complete-mouth rehabilitation: a clinical report.

Dental fluorosis results from excess fluoride ingestion during tooth formation and is commonly seen in certain endemic areas. Its clinical manifestations may range from white opaque patches of enamel in mild cases to pitting and loss of enamel in severe cases. The treatment of fluorosis is important not only because of esthetic and functional concerns but also to help improve a patient's self-esteem; therefore, a multidisciplinary approach is often necessary. This article describes a multidisciplinary approach to complete-mouth rehabilitation of a patient affected with fluorosis. A confluence of the endodontic, periodontal, orthodontic, and prosthodontic disciplines resulted in improved esthetics and enhanced masticatory efficiency.

Exact distributions for stochastic gene expression models with bursting and feedback.

Stochasticity in gene expression can give rise to fluctuations in protein levels and lead to phenotypic variation across a population of genetically identical cells. Recent experiments indicate that bursting and feedback mechanisms play important roles in controlling noise in gene expression and phenotypic variation. A quantitative understanding of the impact of these factors requires analysis of the corresponding stochastic models. However, for stochastic models of gene expression with feedback and bursting, exact analytical results for protein distributions have not been obtained so far. Here, we analyze a model of gene expression with bursting and feedback regulation and obtain exact results for the corresponding protein steady-state distribution. The results obtained provide new insights into the role of bursting and feedback in noise regulation and optimization. Furthermore, for a specific choice of parameters, the system studied maps on to a two-state biochemical switch driven by a bursty input noise source. The analytical results derived provide quantitative insights into diverse cellular processes involving noise in gene expression and biochemical switching.

Gastric Antral Vascular Ectasia.

Iron deficiency anaemia secondary to gastrointestinal bleeding is very common in the elderly. Gastric antral vascular ectasia (GAVE) syndrome, also known as watermelon stomach is an uncommon but significant cause of acute or chronic gastrointestinal blood loss in the elderly. It is characterised endoscopically by "watermelon stripes." It is more common in females than males, and manifests mostly as iron deficiency anaemia due to the gradual blood loss. Pathogenesis is unknown though several humoral factors have been proposed. Diagnosis is based on the clinical history and endoscopic appearance and histological changes. We describe elderly patient who presented with haematemesis and iron deficiency anaemia and was diagnosed to have GAVE and was treated successfully with endoscopic band ligation.

HIV associated Burkitt's lymphoma.

Burkitt's lymphoma (BL) is a highly aggressive B-cell non-Hodgkin Lymphoma (NHL) associated with chromosomal translocations resulting in upregulation of the proto-oncogene C-MYC, which drives progression through the cell cycle NHL accounts for approximately one third of AIDS-related malignancies and the frequency of BL is 2.4-20% of HIV-associated NHL. The outcome of HIV-associated non-Hodgkin lymphoma (NHL) has improved substantially in the highly active antiretroviral therapy (HAART) era. However, HIV-Burkitt lymphoma (BL), which accounts for up to 20% of HIV-NHL, still has poor outcome with standard chemotherapy. We present here a 26 years old female who presented with congestive cardiac failure and sudden onset paraparesis and was finally diagnosed to have right atrial mass and had extradural lesion extending from L2 to S1 which turned out to be High grade NHL-Burkitt's Lymphoma.

Efficacy and Safety of adjunctive Perampanel in a prospective, real-world, Phase IV study in Indian patients aged ≥12 years for Treatment of focal-onset Epilepsy: Study 508.

OBJECTIVE: ESPRITE (Study 508; NCT03836924) evaluated the real-world safety, tolerability, and efficacy of adjunctive perampanel in patients aged ≥12 years with focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS), in India. METHODS: ESPRITE was a prospective, multicenter, single-arm, observational, Phase IV study with a 6-month Treatment Period. Patients were aged ≥12 years and had been prescribed perampanel for adjunctive treatment of FOS, with or without FBTCS. Assessments included incidence of treatment-emergent adverse events (TEAEs; primary endpoint), median percent reduction in seizure frequency per 28 days from baseline, 50% responder rates, and seizure-freedom rates. RESULTS: Overall, 200 patients were enrolled (199 patients in the Safety Analysis Set and 174 patients who completed all visits in the main efficacy analyses). TEAEs (all mild or moderate in severity) were reported in 18.1% (n = 36/199) of patients (the most common were dizziness [3.0%] and irritability [2.0%]). TEAEs leading to discontinuation of perampanel were reported in 2.0% of patients; no deaths or serious TEAEs occurred. At 6 months, median percent reduction in seizure frequency was 100.0%, 50% responder rate was 83.3%, and seizure-freedom rate was 49.4%. SIGNIFICANCE: Adjunctive perampanel (at a mean daily dose of 4 mg/day) was shown to be well tolerated and effective in patients aged ≥12 years with FOS, with or without FBTCS, from India. PLAIN LANGUAGE SUMMARY: Many patients do not receive adequate treatment for epilepsy and need effective seizure control medications. In this 6-month clinical study, 199 patients from India, aged 12 years or older, added perampanel to the anti-seizure medications they were already taking. At 6 months, 49% of patients experienced no seizures since starting perampanel and seizure frequency was reduced by half in 83% of patients. Side effects occurred in 18% of patients (most commonly dizziness and irritability) and caused 2% to stop perampanel; no deaths were reported. Perampanel was an effective and generally safe added medication for patients with epilepsy from India.