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Background: The importance of oral hygiene maintenance is of prime importance in dentulous and edentulous individuals. There are numerous types of bacteria which colonise in the oral cavity. Completely edentulous individuals have to follow proper hygiene procedures to keep their dentures germ free which can prevent numerous oral conditions. The main aim of this text was to briefly understand the interaction between microorganisms and denture, discuss the various methods of preventing plaque formation on dentures and highlight the natural antimicrobial agents in detail. Main body: There are numerous factors which play a role in biofilm formation. Methods such as patient education, maintenance of denture hygiene and use of pharmacological methods have proven to effectively reduce or prevent the growth of microorganisms. Pharmacological agents can broadly be classified into natural and synthetic based on their source of origin. Based on their mechanism of action, they are classified as biocides, biocide releasing polymers and surface acting agents. The use of natural v/s synthetic products has always seen positives and negatives. Apart from the antimicrobial activity, the influence of these agents on the mechanical properties also remains an important aspect. This text highlights the various natural antimicrobial agents that can be incorporated in the dentures and the effect they have on the mechanical properties of the dentures. Conclusion: The interaction between microorganisms and denture has been explored in detail. The various natural and synthetic antimicrobial agents have been enlisted following which the natural antimicrobials have been discussed in detail. The various natural products have shown marked antimicrobial nature however, their influence on the mechanical properties is lacking. [ABSTRACT FROM AUTHOR]

Mass spectrometry-coupled cellular thermal shift assay (MS-CETSA), a biophysical principle-based technique that measures the thermal stability of proteins at the proteome level inside the cell, has contributed significantly to the understanding of drug mechanisms of action and the dissection of protein interaction dynamics in different cellular states. One of the barriers to the wide applications of MS-CETSA is that MS-CETSA experiments must be performed on the specific cell lines of interest, which is typically time-consuming and costly in terms of labeling reagents and mass spectrometry time. In this study, we aim to predict CETSA features in various cell lines by introducing a computational framework called CycleDNN based on deep neural network technology. For a given set of n cell lines, CycleDNN comprises n auto-encoders. Each auto-encoder includes an encoder to convert CETSA features from one cell line into latent features in a latent space Z . It also features a decoder that transforms the latent features back into CETSA features for another cell line. In such a way, the proposed CycleDNN creates a cyclic prediction of CETSA features across different cell lines. The prediction loss, cycle-consistency loss, and latent space regularization loss are used to guide the model training. Experimental results on a public CETSA dataset demonstrate the effectiveness of our proposed approach. Furthermore, we confirm the validity of the predicted MS-CETSA data from our proposed CycleDNN through validation in protein–protein interaction prediction. [ABSTRACT FROM AUTHOR]

Cellular phenotypes of apoptosis, as well as the activation of apoptosis caspase cascades, are well described. However, sequences and locations of early biochemical effector events after apoptosis initiation are still only partly understood. Here, we use integrated modulation of protein interaction states-cellular thermal shift assay (IMPRINTS-CETSA) to dissect the cellular biochemistry of early stages of apoptosis at the systems level. Using 5 families of cancer drugs and a new CETSA-based method to monitor the cleavage of caspase targets, we discover the initial biochemistry of the effector stage of apoptosis for all the studied drugs being focused on the peripheral nuclear region rather than the cytosol. Despite very different candidate apoptosis-inducing mechanisms of the drug families, as revealed by the CETSA data, they converge into related biochemical modulations in the peripheral nuclear region. This implies a higher control of the localization of the caspase cascades than previously anticipated and highlights the nuclear periphery as a critical vulnerability for cancer therapies. [Display omitted] • IMPRINTS-CETSA reveals drug-specific and converging mechanisms of apoptotic drugs • The initial effector phase of apoptosis is focused on the peripheral nuclear region • Regional stabilization after proteolysis (RESP) identifies proteolytic events in living cells IMPRINTS-CETSA reveals that apoptosis-inducing drugs with distinct mechanisms converge into biochemical modulations in the peripheral nuclear region. We were able to identify proteolytic events in living cells by a phenomenon we call regional stabilization after proteolysis (RESP), where specific parts of the protein get stabilized. [ABSTRACT FROM AUTHOR]

Esthetics remain an inseparable aspect affecting the mental health of a person. On losing teeth, patients suffer from a lack of confidence, and in the majority of cases, it affects their mental well-being. Mental health and social interaction are integral entities for evaluating the quality of life. A prosthodontist should aim to provide the best possible version of rehabilitation to the patient. However, constraints such as affordability, willingness, and acceptance of the patient always affect the suggested treatment plan. Many modifications have been done previously using attachments on the complete denture but not on a removable partial denture. This case report demonstrates a patient who was partially edentulous, had sunken cheeks, and was concerned about her facial appearance. In the presented case, an alternative method of the fabrication of cheek plumper on a removable partial denture was done to provide an esthetic restoration. For the construction of the prosthesis, a lumbar puncture needle was used, which was soldered to Adams clasps, to support the cheek plumper on the removable partial denture. The prosthesis improved the facial shape of the patient and provided a youthful appearance. The patient was happy and contented with the treatment outcome. [ABSTRACT FROM AUTHOR]

Microstomia is a term used for reduced mouth opening; it can be associated with congenital or acquired conditions. Oral cavity is an entrance to the rest of the body, and a disability in this crucial area leads to impaired function, psychology, and esthetics. Microstomia is one such condition which not only hampers the patient's physical well-being but also mental tranquility. The rehabilitation in such patients should offer them functional demand with esthetics and elevate their quality of life. It is a responsibility of a prosthodontist to meet such challenges as these patients face difficulty in inserting as well as removing the dentures and the problem aggravates with age as the manual dexterity reduces. This clinical report demonstrates a case of a completely edentulous female who underwent radiation therapy of the head. This article presents a simple yet effective approach for rehabilitation of a microstomia patient with the fabrication of collapsible denture using a silicone-based permanent soft denture liner. [ABSTRACT FROM AUTHOR]

Small‐molecule drugs modulate biological processes and disease states through engagement of target proteins in cells. Assessing drug–target engagement on a proteome‐wide scale is of utmost importance in better understanding the molecular mechanisms of action of observed beneficial and adverse effects, as well as in developing next generation tool compounds and drugs with better efficacies and specificities. However, systematic assessment of drug–target engagement has been an arduous task. With the continuous development of mass spectrometry‐based proteomics instruments and techniques, various chemical proteomics approaches for drug target deconvolution (i.e., the identification of molecular target for drugs) have emerged. Among these, the label‐free target deconvolution approaches that do not involve the chemical modification of compounds of interest, have gained increased attention in the community. Here we provide an overview of the basic principles and recent biological applications of the most important label‐free methods including the cellular thermal shift assay, pulse proteolysis, chemical denaturant and protein precipitation, stability of proteins from rates of oxidation, drug affinity responsive target stability, limited proteolysis, and solvent‐induced protein precipitation. The state‐of‐the‐art technical implications and future outlook for the label‐free approaches are also discussed. [ABSTRACT FROM AUTHOR]

The paper seeks to address issues that arise during the drilling and fixation of bones in orthopedic, orthodontic and implant surgeries. Thermal necrosis is one of the widespread problems that occurs during bone/tooth drilling and which can lead to implant failures. The highest registered temperature during drilling is 86°C. However, when the temperature is increased beyond 47° C during the drilling process, it can often lead to osteonecrosis. The possibility of thermal necrosis can be minimized by controlling the drilling parameters. However, optimal parameter values identified by various researchers have not been complied so far, primarily because of the effects of multifactorial constraints. Overall, the drilling bore speed and the feed rate are found to be the most influential parameters in triggering thermal injuries in the course of time. The drilling speed is also more important to the feed rate. In addition, osteological location also increases the probability of necrosis by multiple means in terms of anatomy. A thermocouple is used to evaluate in vivo temperature conditions during the drilling process. However, given the uncertainty and the practical errors that occur during the experimental measurements, the finite-element analysis (FEA) is proposed in most studies. This paper explores the existing state of literature and summarizes various drilling methods and assess the related parameters using FEA. It also describes the impact of various constraints in detail to explore the optimum drilling parameters in order to minimize the danger of thermal necrosis. [ABSTRACT FROM AUTHOR]

Replacing a single or multiple tooth pose various clinical challenges to the clinician during prosthetic rehabilitation. This clinical challenge is more complicated with fixed dental prosthesis when there is an insufficient space for the pontic. Replacing the tooth in these quantifiable situation is best suited by implant supported prosthesis. In the presented case series, we present three such cases where missing teeth were restored with implant supported prosthesis immediately post extraction to satisfy patients aesthetic as well as functional needs. [ABSTRACT FROM AUTHOR]

Patients afflicted with congenital cleft lip defect experience disfigured facial esthetics and lack of oral competency that could reduce the speech intelligibility. Rehabilitation of such cosmetic deformities condition often encountered with dental abnormalities becomes the challenge. When surgical treatment is not desired, prosthetic reconstruction turns out to be an economical option. This clinical treatment describes the fabrication of a maxillary lip prosthesis supported by a cast partial denture retained with magnetic attachment in a cleft lip patient. The use of intraoral magnets placed labially on the cast partial denture and on the counterpart of the prosthesis improved the retention. Moreover, the biomedical-grade silicone prosthesis used to blend closely with the patient's skin shade fulfilled the esthetic needs. [ABSTRACT FROM AUTHOR]

The cellular thermal shift assay (CETSA) is a biophysical technique allowing direct studies of ligand binding to proteins in cells and tissues. The proteome-wide implementation of CETSA with mass spectrometry detection (MS-CETSA) has now been successfully applied to discover targets for orphan clinical drugs and hits from phenotypic screens, to identify off-targets, and to explain poly-pharmacology and drug toxicity. Highly sensitive multidimensional MS-CETSA implementations can now also access binding of physiological ligands to proteins, such as metabolites, nucleic acids, and other proteins. MS-CETSA can thereby provide comprehensive information on modulations of protein interaction states in cellular processes, including downstream effects of drugs and transitions between different physiological cell states. Such horizontal information on ligandmodulation in cells is largely orthogonal to vertical information on the levels of different proteins and therefore opens novel opportunities to understand operational aspects of cellular proteomes. [ABSTRACT FROM AUTHOR]

Intraoral periapical radiography and panoramic radiography used to be indispensable tools for hard tissue analysis in dental implant planning. However, their inherent 2D limitations have ushered in an era of Cone Beam Computed Tomography (CBCT) for a volumetric holistic analysis. This case report depicts accidental displacement of implant into a mandibular medullary bone space with deficient bone density in an otherwise healthy individual and its subsequent surgical retrieval and prognosis. We wish to highlight the importance of CBCT as a mandatory pre-surgical tool for implant planning in all cases to prevent intraoperative adverse events, irrespective of their medical status. [ABSTRACT FROM AUTHOR]

The method of horizontal bone augmentation using ridge split and expansion was introduced by Dr. Hilt Tatum about 30 years ago, and it has been followed since then. Though there are many methods available for horizontal bone augmentation, ridge split and expansion has been used widely. In this case report we describe a case of horizontal ridge augmentation using ridge expansion along with simultaneous implant placement in esthetic maxillary anterior region. [ABSTRACT FROM AUTHOR]

Metabolite-protein interactions define the output of metabolic pathways and regulate many cellular processes. Although diseases are often characterized by distortions in metabolic processes, efficient means to discover and study such interactions directly in cells have been lacking. A stringent implementation of proteome-wide Cellular Thermal Shift Assay (CETSA) was developed and applied to key cellular nucleotides, where previously experimentally confirmed protein-nucleotide interactions were well recaptured. Many predicted, but never experimentally confirmed, as well as novel protein-nucleotide interactions were discovered. Interactions included a range of different protein families where nucleotides serve as substrates, products, co-factors or regulators. In cells exposed to thymidine, a limiting precursor for DNA synthesis, both dose- and time-dependence of the intracellular binding events for sequentially generated thymidine metabolites were revealed. Interactions included known cancer targets in deoxyribonucleotide metabolism as well as novel interacting proteins. This stringent CETSA based strategy will be applicable for a wide range of metabolites and will therefore greatly facilitate the discovery and studies of interactions and specificities of the many metabolites in human cells that remain uncharacterized. [ABSTRACT FROM AUTHOR]

Introduction: In spite of being proven a promising material of choice as a denture base material, the fracture resistance of conventional poly methyl methacrylate could be enhanced. Aim: This in vitro study was conducted to evaluate and compare the flexural strengths of three types of commercially available heat cure, high impact denture base resins reinforced with either silver nanoparticles or E-glass fibres. Materials and Methods: Three commercially available heat cures, high impact denture base resins (Trevalon HI-Dentsply, Acryl H - PyraxPolymars and Acralyn H - Asian Acrylates) were selected for the study. The three types of resins were further subdivided into three subgroups (Control group, Resin incorporated with 0.5% silver nanoparticles and Resin incorporated with 2% E-glass fibres) of 10 samples each achieving a total of 90 samples. The samples were subjected to a 3-point bending test for evaluation of flexural strength. The data were analysed using one-way ANOVA. Results: Acralyn H resin group showed the highest result for mean flexural strength for all the three subgroups. There was an increase in the flexural strength of Trevalon HI and Acralyn H resin groups on addition of either silver nanoparticles (AgNPs) or E-glass fibres (p<0.05), but a decrease in flexural strength on addition of AgNPs to Acryl H resin group and negligible change on addition of E-glass fibres. Difference in flexural strength between the three types of materials was observed but there was no significant difference in between the subgroups of each type of denture base resin except type 2 (Trevalon HI-Dentsply) where a significant change was observed. Conclusion: The addition of E-glass fibres or silver nanoparticles causes a change in flexural properties of high impact, heat cure denture base resins. However, the change in mechanical properties is highly dependent on the brand of material used. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated and compared the surface roughness achieved by glazing porcelain samples in a conventional and a microwave oven.Materials and Methods: Two commercial brands of metal ceramics were used, VITA VMK MASTER and IPS CLASSIC. Sixty samples were fabricated, 30 for each type of ceramic. The samples were sintered in the conventional oven and hand-polished to remove any irregularities. Samples (n = 10) from each type of ceramic were further divided into three groups as follows: hand-polished (Group A), conventional oven glazed (Group B), and microwave glazed (Group C). Each specimen was evaluated for surface roughness by atomic force microscope. Data were statistically analyzed using two-way analysis of variance (ANOVA) and Tukey's post hoc test (a = 0.05).Results: Two-way ANOVA indicated a highly significant difference in surface roughness based on the type of glazing (P < 0.001), there was a significant difference based on the metal ceramics (P = 0.002). There was also a significant interaction between the type of glazing and metal ceramics (P = 0.009). The images obtained from the atomic force microscope corroborated the measured values.Conclusions: All the results indicate that microwave glazing can be a feasible option for glazing porcelain specimens. It was concluded that surface topography is influenced by surface treatment and microwave glazed ceramic is superior to conventional oven glazed ceramic and hand-polishing showed greater surface roughness when compared to glazing. IPS CLASSIC ceramic showed relatively smooth surface when compared to VITA VMK MASTER irrespective of the surface treatment. [ABSTRACT FROM AUTHOR]

Influenza and asthma are two of the major public health concerns in the world today. During the 2009 influenza pandemic asthma was found to be the commonest comorbid illness of patients admitted to hospital. Unexpectedly, it was also observed that asthmatic patients admitted to hospital with influenza infection were less likely to die or require admission to intensive care compared with non-asthmatics. Using an in vivo model of asthma and influenza infection we demonstrate that prior exposure to Blomia tropicalis extract (BTE) leads to an altered immune response to influenza infection, comprised of less severe weight loss and faster recovery following infection. This protection was associated with significant increases in T cell numbers in the lungs of BTE sensitised and infected mice, as well as increased IFN-γ production from these cells. In addition, elevated numbers of CD11b+ dendritic cells (DCs) were found in the lung draining lymph nodes following infection of BTE sensitised mice compared to infected PBS treated mice. These CD11b+ DCs appeared to be better at priming CD8 specific T cells both in vivo and ex vivo, a function not normally attributed to CD11b+ DCs. We propose that this alteration in cross-presentation and more efficient T cell priming seen in BTE sensitised mice, led to the earlier increase in T cells in the lungs and subsequently faster clearance of the virus and reduced influenza induced pathology. We believe this data provides a novel mechanism that explains why asthmatic patients may present with less severe disease when infected with influenza. [ABSTRACT FROM AUTHOR]

Achieving robust cancer-specific lethality is the ultimate clinical goal. Here, we identify a compound with dual-inhibitory properties, named a131, that selectively kills cancer cells, while protecting normal cells. Through an unbiased CETSA screen, we identify the PIP4K lipid kinases as the target of a131. Ablation of the PIP4Ks generates a phenocopy of the pharmacological effects of PIP4K inhibition by a131. Notably, PIP4Ks inhibition by a131 causes reversible growth arrest in normal cells by transcriptionally upregulating PIK3IP1, a suppressor of the PI3K/Akt/mTOR pathway. Strikingly, Ras activation overrides a131-induced PIK3IP1 upregulation and activates the PI3K/Akt/mTOR pathway. Consequently, Ras-transformed cells override a131-induced growth arrest and enter mitosis where a131's ability to de-cluster supernumerary centrosomes in cancer cells eliminates Ras-activated cells through mitotic catastrophe. Our discovery of drugs with a dual-inhibitory mechanism provides a unique pharmacological strategy against cancer and evidence of cross-activation between the Ras/ Raf/MEK/ERK and PI3K/AKT/mTOR pathways via a Ras-PIK3IP1-PI3K signaling network. [ABSTRACT FROM AUTHOR]

CD8+ T cells play an important role in providing protective immunity against a wide range of pathogens, and a number of different factors control their activation. Although CD40L-mediated CD40 licensing of dendritic cells (DCs) by CD4+ T cells is known to be necessary for the generation of a robust CD8+ T cell response, the contribution of CD8+ T cell-expressed CD40L on DC licensing is less clear. We have previously shown that CD8+ T cells are able to induce the production of IL-12 p70 by DCs in a CD40L- dependent manner, providing some evidence that CD8+ T cell-mediated activation of DCs is possible. To better understand the role of CD40L on CD8+ T cell responses, we generated and characterized CD40L-expressing CD8+ T cells both in vitro and in vivo. We found that CD40L was expressed on 30-50% of effector CD8+ T cells when stimulated and that this expression was transient. The expression of CD40L on CD8+ T cells promoted the proliferation and differentiation of both the CD40L-expressing CD8+ T cells and the bystander effector CD8+ T cells. This process occurred via a cell-extrinsic manner and was mediated by DCs. These data demonstrate the existence of a mechanism where CD8+ T cells and DCs cooperate to maximize CD8+ T cell responses. [ABSTRACT FROM AUTHOR]

Blomia tropicalis is the major asthma allergen in the tropics comparable to Dermatophagoides pteronyssinus. However, little is known about the B. tropicalis epitopes recognized by T cells. Our aim was to identify the T-cell epitopes in the major B. tropicalis allergen, Blo t 5, and investigate the potential of the corresponding peptides to inhibit the allergic inflammatory lung response. C57 BL/6 mice were immunized with plasmid DNA encoding Blo t 5 and T-cell epitopes identified using the interferon- γ ELISPOT assay with 15-mer overlapping peptides. C57 BL/6 mice were sensitized with bone-marrow-derived dendritic cells ( BMDC) pulsed with Blo t 5 allergen followed by intranasal Blo t 5 challenge. Two H-2b restricted epitopes (Bt576-90 and Bt5106-115) were recognized by CD4 T cells specific for Blo t 5, but no CD8 epitopes were identified. In mice sensitized with Blo t 5-pulsed BMDC and challenged with intranasal Blo t 5 Bt576-90 and Bt5106-115, peptide-specific CD4 T cells were found to secrete the T helper type 2 cytokines interleukin-5 and interleukin-13. Intradermal administration of synthetic peptides encoding the identified T-cell epitopes suppressed allergic airway inflammation to further allergen challenges. Hence, we have identified novel CD4 T-cell epitopes specific for Blo t 5 and demonstrated that these peptides could be employed therapeutically to suppress the T-cell response in a murine model of allergic airway inflammation. [ABSTRACT FROM AUTHOR]

The restoration of normal function and esthetics is often challenging in the prosthetic rehabilitation of patients with hemimandibulectomy defects due to unstable occlusion and mandibular deviation. The extensive period of time for completion of healing of the reconstructed mandible through reconstructive plastic surgery and/or implant-assisted prosthesis may compromise the masticatory function by causing delay in the fabrication of definitive prosthesis. This case report describes a novel technique for the construction of customized attachment-retained mandibular guiding flange prosthesis for immediate rectification of the frontal plane rotation occurring after hemimandibulectomy. [ABSTRACT FROM AUTHOR]

The success of an ocular prosthesis depends largely on the correct orientation of the iris disk. Various methods have been put forth to achieve this. This article emphasizes one such simplified method, wherein a customized scale has been used to orient the iris disk mediolaterally, superoinferiorly, and anteroposteriorly in an ocular prosthesis. A scleral wax pattern was fabricated. The customized scale was used to measure the dimension and orientation of the natural iris. These measurements were then transferred to the scleral wax pattern with the customized scale. An iris disk was fabricated using black crayon on the scleral wax pattern according to the measurements. The scleral wax pattern, including the iris disk, was then placed in the eye socket to verify its dimension and orientation. A prefabricated iris disk was modified according to the measured dimensions and transferred to the final scleral wax pattern. The transfer of these dimensions to the definitive prosthesis was achieved successfully, ultimately improving the patient's social and psychological well being. [ABSTRACT FROM AUTHOR]

Background: Given that there is a possibility of a human H5N1 pandemic and the fact that the recent H5N1 viruses are resistant to the anti-viral drugs, newer strategies for effective therapy are warranted. Previous studies show that single mAbs in immune prophylaxis can be protective against H5N1 infection. But a single mAb may not be effective in neutralization of a broad range of different strains of H5N1 and control of potential neutralization escape mutants. Methods/Principal Findings: We selected two mAbs which recognized different epitopes on the hemagglutinin molecule. These two mAbs could each neutralize in vitro escape mutants to the other and in combination could effectively neutralize viruses from clades 0, 1, 2.1, 2.2, 2.3, 4, 7 and 8 of influenza A H5N1 viruses. This combination of chimeric mAbs when administered passively, pre or post challenge with 10 MLD50 (50% mouse lethal dose) HPAI H5N1 influenza A viruses could protect 100% of the mice from two different clades of viruses (clades 1 and 2.1). We also tested the efficacy of a single dose of the combination of mAbs versus two doses. Two doses of the combination therapy not only affected early clearance of the virus from the lung but could completely prevent lung pathology of the H5N1 infected mice. No escape variants were detected after therapy. Conclusions/Significance: Our studies provide proof of concept that the synergistic action of two or more mAbs in combination is required for preventing the generation of escape mutants and also to enhance the therapeutic efficacy of passive therapy against H5N1 infection. Combination therapy may allow for a lower dose of antibody to be administered for passive therapy of influenza infection and hence can be made available at reduced economic costs during an outbreak. [ABSTRACT FROM AUTHOR]

Background: Human infections with highly pathogenic H5N1 avian influenza viruses have generally been confirmed by molecular amplification or culture-based methods. Serologic surveillance has potential advantages which have not been realized because rapid and specific serologic tests to detect H5N1 infection are not widely available. Methodology/Principal Findings: Here we describe an epitope-blocking ELISA to detect specific antibodies to H5N1 viruses in human or animal sera. The assay relies on a novel monoclonal antibody (5F8) that binds to an epitope comprising amino acid residues 274-281 (CNTKCQTP) in the HA1 region of H5 hemagglutinin. Database search analysis of publicly available sequences revealed that this epitope is conserved in 100% of the 163 H5N1 viruses isolated from humans. The sensitivity and specificity of the epitope-blocking ELISA for H5N1 were evaluated using chicken antisera to multiple virus clades and other influenza subtypes as well as serum samples from individuals naturally infected with H5N1 or seasonal influenza viruses. The epitope-blocking ELISA results were compared to those of hemagglutinin inhibition (HI) and microneutralization assays. Antibodies to H5N1 were readily detected in immunized animals or convalescent human sera by the epitopeblocking ELISA whereas specimens with antibodies to other influenza subtypes yielded negative results. The assay showed higher sensitivity and specificity as compared to HI and microneutralization. Conclusions/Significance: The epitope-blocking ELISA based on a unique 5F8 mAb provided highly sensitive and 100% specific detection of antibodies to H5N1 influenza viruses in human sera. [ABSTRACT FROM AUTHOR]

Edentulousness falls in a special category among the various conditions of dental origin. Tooth loss is the dental equivalent of mortality. A simple estimation of the proportion of the partial edentulous persons is a rough indication of the prevalence of dental diseases and the success or failure of dental care. The epidemiological features of partial edentulousness of one community or one village can be evaluated on the basis of a cross-sectional house-to-house survey. In this study a crosssectional house-to-house survey was carried out at Herga village of Udupi District, Karnataka, India. The aim of this study is to evaluate the epidemiological features of partial edentulousness in the age group of 35-44 years in a rural population based on the Kennedy classification. Chi-square test was conducted and results were obtained and P value < 0.05 was considered statistically significant. [ABSTRACT FROM AUTHOR]

Cranial defects occur most frequently during wartime, but their incidence during peace time, as a result of accident or disease, makes knowledge of cranioplasty useful to the interested practitioner. Trauma accounts for most of the cranial defects. Numerous materials have been historically employed for the restoration of cranial defects. Heat-polymerized methyl methacrylate alloplastic cranial implant requires presurgical fabrication of the implants. It facilitates the reproduction of the contours, and the tissue bed is not exposed to the heat of polymerization or to the free monomer. In this study, a case report has been presented in which heat-cured acrylic resin alloplastic implant has been fabricated for a patient with left frontal bone defect. [ABSTRACT FROM AUTHOR]

A cellular thermal shift assay (CETSA) protocol identifies and resolves antimalarial drug targets in P. falciparum. Defining drug targets in malaria: Different classes of malaria drugs have been used for decades, even though the mechanisms of action have never been elucidated. To identify antimalarial drug targets, Dziekan et al. developed a protocol combining mass spectrometry and cellular thermal shift assay. The assay uses parasite lysate and intact infected red blood cells and was able to positively identify two known drug targets. They then investigated targets for quinine and mefloquine, revealing purine nucleoside phosphorylase as the top hit. Their results not only identify the likely target of these common drugs but also showcase an assay that could be widely used in antimalarial drug research. Mechanisms of action (MoAs) have been elusive for most antimalarial drugs in clinical use. Decreasing responsiveness to antimalarial treatments stresses the need for a better resolved understanding of their MoAs and associated resistance mechanisms. In the present work, we implemented the cellular thermal shift assay coupled with mass spectrometry (MS-CETSA) for drug target identification in Plasmodium falciparum, the main causative agent of human malaria. We validated the efficacy of this approach for pyrimethamine, a folic acid antagonist, and E64d, a broad-spectrum cysteine proteinase inhibitor. Subsequently, we applied MS-CETSA to quinine and mefloquine, two important antimalarial drugs with poorly characterized MoAs. Combining studies in the P. falciparum parasite lysate and intact infected red blood cells, we found P. falciparum purine nucleoside phosphorylase (PfPNP) as a common binding target for these two quinoline drugs. Biophysical and structural studies with a recombinant protein further established that both compounds bind within the enzyme's active site. Quinine binds to PfPNP at low nanomolar affinity, suggesting a substantial contribution to its therapeutic effect. Overall, we demonstrated that implementation of MS-CETSA for P. falciparum constitutes a promising strategy to elucidate the MoAs of existing and candidate antimalarial drugs. [ABSTRACT FROM AUTHOR]