Conventional and Digital Impressions for Fabrication of Complete Implant-Supported Bars: A Comparative In Vitro Study.

Obtaining accurate models and well-fitting prostheses during the fabrication of complete implant-supported prostheses has been a significant challenge. Conventional impression methods involve multiple clinical and laboratory steps that can lead to distortions, potentially resulting in inaccurate prostheses. In contrast, digital impressions may eliminate some of these steps, leading to better-fitting prostheses. Therefore, it is important to compare conventional and digital impressions for producing implant-supported prostheses. This study aimed to compare the quality of digital intraoral and conventional impressions by measuring the vertical misfit of implant-supported complete bars obtained using both types of techniques. Five digital impressions using an intraoral scanner and five impressions using elastomer were made in a four-implant master model. The plaster models produced with conventional impressions were scanned in a laboratory scanner to obtain virtual models. Screw-retained bars (n = five) were designed on the models and milled in zirconia. The bars fabricated using digital (DI) and conventional (CI) impressions were screwed to the master model, initially with one screw (DI1 and CI1) and later with four screws (DI4 and CI4), and were analyzed under a SEM to measure the misfit. ANOVA was used to compare the results (p < 0.05). There were no statistically significant differences in the misfit between the bars fabricated using digital and conventional impressions when screwed with one (DI1 = 94.45 µm vs. CI1 = 101.90 µm: F = 0.096; p = 0.761) or four screws (DI4 = 59.43 µm vs. CI4 = 75.62 µm: F = 2.655; p = 0.139). Further, there were no differences when the bars were compared within the same group screwed with one or four screws (DI1 = 94.45 µm vs. DI4 = 59.43 µm: F = 2.926; p = 0.123; CI1 = 101.90 µm vs. CI4 = 75.62 µm: F = 0.013; p = 0.907). It was concluded that both impression techniques produced bars with a satisfactory fit, regardless of whether they were screwed with one or four screws.

Label free, electric field mediated ultrasensitive electrochemical point-of-care device for CEA detection.

Developing point-of-care (PoC) diagnostic platforms for carcinoembryonic antigen detection is essential. However, thefew implementations of transferring the signal amplification strategies in electrochemical sensing on paper-based platforms are not satisfactory in terms of detection limit (LOD). In the quest for pushing down LOD, majority of the research has been targeted towards development of improved nanostructured substrates for entrapping more analyte molecules and augmenting the electron transfer rate to the working electrode. But, such approaches have reached saturation. This paper focuses on enhancing the mass transport of the analyte towards the sensor surface through the application of an electric field, in graphene-ZnO nanorods heterostructure. These hybrid nanostructures have been deposited on flexible polyethylene terephthalate substrates with screen printed electrodes for PoC application. The ZnO nanorods have been functionalized with aptamers and the working sensor has been integrated with smartphone interfaced indigenously developed low cost potentiostat. The performance of the system, requiring only 50 µl analyte has been evaluated using electrochemical impedance spectroscopy and validated against commercially available ELISA kit. Limit of detection of 1 fg/ml in human serum with 6.5% coefficient of variation has been demonstrated, which is more than three orders of magnitude lower than the existing attempts on PoC device.

Dopamine Receptor D1 Contributes to Cocaine Epigenetic Reprogramming of Histone Modifications in Male Germ Cells.

Paternal environmental perturbations, including cocaine intake, can affect the development and behavior of the offspring through epigenetic inheritance. However, the mechanism by which cocaine alters the male germ cells epigenome is almost unexplored. Here, we report that cocaine-treated male mice showed alterations on specific histone post-translational modifications (PTMs) including increased silent chromatin marks H3K9me3 and H3K27me3 and decreased active enhancer and promoter marks H3K27ac and H3K4me3 in isolated germ cells. Also, cocaine increased H3K9ac and H4K16ac levels, involved in the replacement of histones by protamines that take place at round spermatid stage. Cocaine also altered histones H3/H4 epigenetic enzymes by increasing acetyltransferase KAT8/MOF, deacetylase SIRT1 and methyltransferase KMT1C/G9A, and decreasing deacetylases HDAC1/2 and demethylase KDM1A/LSD1 protein levels. Moreover, a pre-treatment with dopamine receptor 1 (DRD1) antagonist SCH23390 (SCH) blocked cocaine effects on H3K4me3, H3K27me3, and H4K16ac epigenetic marks. Interestingly, treatment with SCH-only was able to modify most of the histone marks tested here, pointing to a dopamine role in controlling histone PTMs in germ cells. Taken together, our data suggest a key role for DRD1 in mediating cocaine-triggered epigenetic modifications related to the silencing of gene transcription and the histone-to-protamine replacement that controls chromatin architecture of maturing sperm cells, and pinpoints a novel role of the dopaminergic system in the regulation of male germ cells reprogramming.

Label-Free Biomolecule Detection in Physiological Solutions With Enhanced Sensitivity Using Graphene Nanogrids FET Biosensor.

Recently, graphene nanogrid sensor has been reported to be capable of sub-femtomolar sensing of Hepatitis B (Hep-B) surface antigen in buffer. However, for such low concentration of Hep-B in serum, it has been observed during real-time operation that there is an overlap of around 50% in the drain-source current sensitivity values between different concentrations of the target biomolecule, in the range from 0.1 to 100 fM. This has been attributed to the fact that the concentration of non-specific antigen in serum being significantly higher than that of the target antigen, there is a considerable deviation in the number of captured target antigen for the same concentration. Further, this degree of overlap varies from one set to another set of sensor, depending on the statistical variations in the sensor fabrication process. This phenomenon challenges the quantification of target antigen for ultralow limit in physiological analyte. In this paper, we introduce probabilistic neural network (PNN) for quantification of Hep-B down to 0.1 fM in serum using graphene nanogrids field-effect transistor biosensor. The sensor has been operated in heterodyne mode in the frequency range of 100 kHz to 1 MHz applied between drain and source to overcome the problem of Debye screening effect. The application of PNN limits the quantification error within 10% in the range of 0.1 to 100 fM in contrast to 77% and 66% using polynomial fit and static neural network models, respectively. Further, the proposed methodology lowers the detection limit of Hep-B in serum by more than three orders of magnitude compared with the state-of-the-art, real-time, label-free sensors.

Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors.

To find novel P-gp-inhibitors, a library of pregnane X receptor (PXR) ligands and the ZINC DrugsNow library were superimposed on the P-gp inhibitor (+)-pinoresinol (1) used as a query for a three-dimensional similarity search. After determining the TanimotoCombo index of similarity with 1, eight compounds from the PXR library and two ZINC compounds were selected for biological evaluation. The P-gp inhibition study showed that compounds 7, 8, and 9 successfully increased intracellular doxorubicin (DOX) accumulation in the P-gp overexpressed Lucena 1 cells from 25, 12.5, and 6.25 µM, respectively. Among a series of analogues of 9, compounds 26-30 were shown to be active, with 26 and 27 causing a significant increase in DOX accumulation from 1.56 µM and rendering Lucena 1 sensitive to DOX from 1.56 and 0.78 µM, respectively. Molecular modeling studies showed that both compounds bind to the P-gp at transmembrane helices (TMH) 4, 5, and 6, with 27 also showing contacts with TMH 3.

Quantitative differentiation of multiple virus in blood using nanoporous silicon oxide immunosensor and artificial neural network.

In spite of the rapid developments in various nanosensor technologies, it still remains challenging to realize a reliable ultrasensitive electrical biosensing platform which will be able to detect multiple viruses in blood simultaneously with a fairly high reproducibility without using secondary labels. In this paper, we have reported quantitative differentiation of Hep-B and Hep-C viruses in blood using nanoporous silicon oxide immunosensor array and artificial neural network (ANN). The peak frequency output (fp) from the steady state sensitivity characteristics and the first cut off frequency (fc) from the transient characteristics have been considered as inputs to the multilayer ANN. Implementation of several classifier blocks in the ANN architecture and coupling them with both the sensor chips, functionalized with Hep-B and Hep-C antibodies have enabled the quantification of the viruses with an accuracy of around 95% in the range of 0.04fM-1pM and with an accuracy of around 90% beyond 1pM and within 25nM in blood serum. This is the most sensitive report on multiple virus quantification using label free method.

Protection of spermatogenesis in mice against gamma ray induced damage by Hippophae rhamnoides.

The radioprotective action of a preparation from Hippophae rhamnoides berries RH-3, already reported to render >80% survival against whole body 10 Gy gamma irradiation, was further investigated with respect to the testicular system. RH-3 was administered to mice 30 min before gamma irradiation (5 and 10 Gy) and histological parameters such as testis weight, sperm count, frequency of abnormal sperm, repopulation index, stem cell survival index and seminiferous tubular diameter were assessed on the 35th day. RH-3 administration partially countered radiation induced reduction in testis weight, sperm count, repopulation index and stem cell survival index (p < 0.01). The increase in the frequency of abnormal sperm (15.17 +/- 1.046%) caused by irradiation (5 Gy) was counteracted by pre-irradiation treatment with RH-3, which significantly decreased the level of abnormal spermatozoa to 7.99 +/- 0.918% (p < 0.001), i.e. 52% abnormalities in comparison with 5 Gy irradiated group. RH-3 treatment alone did not elicit any toxic or adverse effect on the process of spermatogenesis. The present study suggests that RH-3 treatment protected spermatogenesis by enhancing the spermatogonial proliferation, enhancing the stem cell survival and reducing sperm abnormalities. The presence of polyphenolic flavonoids and tannins in the extract and the radical scavenging activity might be responsible for the radioprotective action of RH-3.

Radioprotective mechanism of Podophyllum hexandrum during spermatogenesis.

RP-1, a herbal preparation of Podophyllum hexandrum has already been reported to provide protection against whole body lethal gamma irradiation (10 Gy). It has also been reported to render radioprotection to germ cells during spermatogenesis. Present study was undertaken to unravel the cellular and molecular mechanism of action of RP-1 on testicular system in strain 'A' mice. Various antioxidant parameters such as thiol content, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) enzyme activity, lipid peroxidation (LPO) and total protein levels were investigated. Thiol content was seen to increase significantly (p < 0.05) in both RP-1 alone and RP-1 pretreated irradiated groups over the irradiated groups at 8, 16 and 24 h. Irradiation (10 Gy) significantly decreased GPx, GST and GR activity in comparison to untreated control but RP-1 treatment before irradiation significantly (p < 0.05) countered radiation-induced decrease in the activity of these enzymes. Radiation-induced LPO was also found to be reduced at all time intervals by RP-1 treatment before irradiation. As compared to irradiated group the protein content in testicular tissue was increased in RP-1 pretreated irradiated group at 4 and 16 h significantly (p < 0.05). Comets revealed by single-cell gel electrophoresis were significantly longer (p < 0.001) in irradiated mice than in unirradiated control. RP-1 treatment before irradiation, however, rendered significant increase (p < 0.05) in comet length over the corresponding control and irradiated group initially at 4 h but at later time points, this was reduced significantly (p < 0.01) as compared to the irradiated group. RP-1 treatment alone rendered shorter comets at 8, 16 and 24 h than irradiated groups (p < 0.001). This study implies that RP-1 offers radioprotection at biochemical and cytogenetic level by protecting antioxidant enzymes, reducing LPO and increasing thiol content.

Enhancement of radiation-induced apoptosis by Podophyllum hexandrum.

The aqueous extract of Podophyllum hexandrum (RP-1), which has been recently reported to manifest radioprotective and anti-tumour properties, has been investigated for its mode of action. RP-1, under in-vitro conditions dose-dependently chelated metal ions, inhibited radiation or metal ion-induced hydroxyl radicals and lipid peroxidation and scavenged superoxide anions. Intraperitoneal administration of RP-1 to mice pre-irradiation (10 Gy) induced more DNA fragmentation and lipid peroxidation in thymocytes maximally at 4 and 8 h, respectively, in comparison with RP-1 treatment or irradiation. Flow-cytometric quantification of sub-diploid peak, oligonucleosomal cleavage assay (ladder) and depletion of total thiols also corroborated the ability of RP-1 to enhance radiation-induced apoptosis. RP-1 in presence of 100 microM CuSO(4) induced strand breaks in plasmid DNA and addition of metal chelators (EDTA and deferoxamine) inhibited the strand scission. Treatment with a major constituent of RP-1, podophyllin, did not cause strand breaks, but isolated constituents of RP-1, quercetin or podophyllotoxin, induced strand breaks. Depending on its concentration in the milieu, RP-1 acted as a pro- or antioxidant modifying the radiation-induced apoptosis and therefore could be exploited for cancer management.

Clinical appraisal of Ascaris lumbricoides, with special reference to surgical complications.

Over a period of 4 years (January 1993-December 1997), 509 patients were treated for abdominal colic with or without intestinal obstruction and a history of passage of adult roundworms either in the stool or in vomitus. All patients were below the age of 10 years, the youngest 6 months old, and were treated successfully with antispasmodics and normal saline enemas. When the pain subsided, an anthelminthic drug was given. Of 209 patients admitted to the hospital, 105 responded to conservative management and 104 (50%) required surgical intervention. The procedures included squeezing out of worms, resection and anastomosis, and treatment of other pathologies like acute appendicitis, tubercular stricture of the small intenstine, etc. Five patients died in the postoperative period due to various complications. There were no deaths among those treated by conservative management. Early recognition of the condition can prevent serious surgical complications and morbidity.

Protection of mouse jejunum against lethal irradiation by Podophyllum hexandrum.

Radiation induced gastrointestinal damage occurs due to the destruction of the clonogenic crypt cells and eventual depopulation and denudation of the villi. P. hexandrum, a plant, known for its antitumour activity, has been shown to protect the mice against whole body lethal (10 Gy) irradiation. Present study was undertaken to investigate the radioprotective effect of P. hexandrum on jejunal villi cells, crypt cells, their proliferative capacity and mitigation of apoptosis. In an in vivo micro colony survival assay, pre-irradiation administration of P. hexandrum (-2 h) increased the number of surviving crypts in the jejunum by a factor of 3.0 (P < 0.05) and villi cellularity by 2.7 (P < 0.05) fold in comparison to irradiated control. Pre-irradiation administration of P. hexandrum reduced the incidence of apoptotic bodies in the crypts (P < 0.05) in a time dependent manner and depicted a mitotic arrest till the 24 h. However, after 84 h the percentage of mitosis was observed to be nearly similar to that of unirradiated control. This study suggests that arrest of cell division may help in protecting the clonogenic cells against radiation. It would be interesting to investigate further the role of P hexandrum in influencing various cell cycle regulators like bcl-2, TGF-beta, Cyclin-E etc.

Selective devascularisation of stomach and lienopulmopexy for prevention of bleedings in portal hypertension in children.

Dissatisfied with different operative procedures for prevention of recurrent bleedings in childhood portal hypertension, many surgeons nowadays treat their patients conservatively during episodic attacks and advocate one of the shunt procedures in adolescence when the splenic vein becomes sufficiently widened (more than 1 cm). Even then mortality cannot be avoided in some bad risk patients especially those living in remote villages lacking facilities for blood transfusion and high speed transport service. In this situation thoracic transposition of spleen and lienopulmopexy was advocated by Nylander and Turumen, Auvert, M. Bettex and others. We prefer a further simpler procedure and perform selective devascularisation of stomach and lienopulmopexy. It allows rapid development of collaterals between splenic pulps on the portal side and subpleural venous plexus on the systemic side to achieve effective gastric devascularisation to prevent further bleeding without hindering the existing portal flow through the liver to avoid the possible occurrence of encephalopathy. Of 21 operated cases one died on the 5th postoperative day and the remaining 20 are doing well. 1/2-5 1/2 years' follow-up revealed negligible morbidity and no recurrence of bleeding in any of them. Both procedures work on the same principle.