Safety of low dose efavirenz regimen in Indian adults with HIV-1 infection: Insights from a phase 4 interventional randomised trial.

BACKGROUND: A randomized interventional phase 4 study in the Indian population confirmed the non-inferiority of the combination tenofovir/lamivudine/efavirenz (TLE)-400 to TLE600. The current manuscript describes in detail the safety profile and patient-reported safety outcomes obtained from the phase 4 study. METHODS: This investigation was part of a phase 4 non-inferiority study with a blinded assessment, conducted across 17 sites in India. The duration of the study was 24 weeks. Safety endpoints assessed included all the adverse events (AEs) related to the study treatment (TLE400 and TLE600). The depression anxiety stress 21-item scale questionnaire and efavirenz-related symptom questionnaire were also used to measure depression, anxiety, stress, and patient experience. RESULTS: A total of 68 patients (52.3%) reported 261 AEs and 87 patients (64.9%) reported 379 AEs related to study treatment in TLE400 group and TLE600 group respectively, P = .037. The reported AEs associated with central nervous system disorders were lower in the TLE400 group with 41 patients (31.5%) to 61 patients (45.5%) in the TLE600 group. The change from mean baseline value for depression anxiety stress 21-item scale at week 28 in TLE400 group and TLE600 group was -5.1 and -6.2 respectively. Similarly, the mean change from baseline score of efavirenz-related symptoms at week 28 in TLE400 group and TLE600 group were -5.1 and -4.1 respectively. CONCLUSION: The low dose efavirenz (400 mg) in combination with tenofovir and lamivudine had a better safety and tolerability profile than the standard dose of efavirenz (600 mg) in combination with tenofovir and lamivudine. Thus, low dose efavirenz should be preferred over the standard dose.

An IoT-based water contamination analysis for aquaculture using lightweight multi-headed GRU model.

Maintaining the quality of water is essential for the health and productivity of aquatic organisms, including fish in aquaculture ponds. However, water contamination can severely impact fish health and survival, making it necessary to develop monitoring systems that can detect early signs of water contamination. Initial deep learning models had limitations in capturing the temporal and spatial dependencies of time-series data, which can lead to inaccurate predictions. In this paper, we propose a smart monitoring system that uses IoT devices to collect water quality data and segment it into contaminated and non-contaminated categories based on a water toxic index (WTI), a measure of water contamination levels. To address the limitations of early deep learning models for classification of toxic and non-toxic water quality, an enhanced light-weight multi-headed gated recurrent unit (MHGRU) model that captures the spatial and temporal dependencies of water quality parameters. Our study demonstrates that the proposed model outperforms existing models, achieving an impressive accuracy of 99.7% when evaluated on real-time data. Notably, our model also excels when tested on a public dataset, achieving an accuracy of 99.12%. In comparison, best performed existing ANN models achieve accuracies of 99.52% and 98.71% on the respective datasets.

Deep reinforcement learning for forecasting fish survival in open aquaculture ecosystem.

Ensuring the classification of water bodies suitable for fish habitat is essential for animal preservation and commercial fish farming. However, existing supervised machine learning models for predicting water quality lack specificity regarding fish survival. This study addresses this limitation and presents a novel model for forecasting fish viability in open aquaculture ecosystems. The proposed model combines reinforcement learning through Q-learning and deep feed-forward neural networks, enabling it to capture intricate patterns and relationships in complex aquatic environments. Moreover, the model's reinforcement learning capability reduces the reliance on labeled data and offers potential for continuous improvement over time. By accurately classifying water bodies based on fish suitability, the proposed model provides valuable insights for sustainable aquaculture management and environmental conservation. Experimental results show a significantly improved accuracy of 96% for the proposed DQN-based model, outperforming existing Gaussian Naive Bayes (78%), Random Forest (86%), and K-Nearest Neighbors (92%) classifiers on the same dataset. These findings highlight the effectiveness of the proposed approach in forecasting fish viability and its potential to address the limitations of existing models.

Patient's Knowledge and Perception of Endodontics Treatment: An Observational Study.

Objective: To assess public awareness regarding endodontic treatment and assess patients' knowledge regarding endodontic treatment. Materials and Methods: A questionnaire was prepared and given to 300 patients who had visited the Department of Conservative Dentistry and Endodontics between November 2021 and October 2022, after obtaining ethical clearance and consent from all the participants. The questionnaire included sociodemographic details and about their knowledge about endodontic treatment. The collected data were tabulated and analyzed. Statistical Analysis: Data analysis was performed using methods of descriptive statistics like frequency and percentages. Results: We found that most of the respondents had an average level of knowledge regarding endodontic treatment. Conclusion: We observed an improvement in knowledge and perception regarding endodontic treatment.

Prediction and detection of emotional tone in online social media mental disorder groups using regression and recurrent neural networks.

Online social media networks have become a significant platform for persons with mental illnesses to discuss their struggles and obtain emotional and informational assistance in recent years. One such platform is Reddit, where sub-groups called 'subreddits' exist, based on a variety of topics including mental illnesses such as anxiety or depression. We analyse the user's interactions to calculate the mental health status by formulating and using a parameter called 'emotional tone' representing the user's emotional state. VADER sentiment analysis and TextBlob are used to categorise emotional tone and find distribution of emotional polarity and subjectivity of comments. For final tone prediction, RNN and State-Of-The-Art word embedding techniques are used to develop a predictive model. The resultant model provides end-to-end categorization and prediction of emotional tone. We obtain results with respect to Weighted L1 Loss that deals with extreme responses. The MODEL transcends all the baselines by at least 12.1% and the final emotional status of the authors is positive.

Application of Convolutional Neural Networks for COVID-19 Detection in X-ray Images Using InceptionV3 and U-Net.

COVID-19 has expanded overall across the globe after its initial cases were discovered in December 2019 in Wuhan-China. Because the virus has impacted people's health worldwide, its fast identification is essential for preventing disease spread and reducing mortality rates. The reverse transcription polymerase chain reaction (RT-PCR) is the primary leading method for detecting COVID-19 disease; it has high costs and long turnaround times. Hence, quick and easy-to-use innovative diagnostic instruments are required. According to a new study, COVID-19 is linked to discoveries in chest X-ray pictures. The suggested approach includes a stage of pre-processing with lung segmentation, removing the surroundings that do not provide information pertinent to the task and may result in biased results. The InceptionV3 and U-Net deep learning models used in this work process the X-ray photo and classifies them as COVID-19 negative or positive. The CNN model that uses a transfer learning approach was trained. Finally, the findings are analyzed and interpreted through different examples. The obtained COVID-19 detection accuracy is around 99% for the best models.

Effect of colchicine and aspirin given together in patients with moderate COVID-19.

Background: The objective of the study was to evaluate the effect of Colchicine 0.5 mg and Aspirin 75 mg oral tablets given together on management of moderate COVID-19. Methods: The study was carried out in 122 moderate COVID-19 patients between ages 40-80 years in hospital, instructed to take either 1 tablet of Colchicine 0.5 mg and Aspirin 75 mg each (treatment group), or 1 tablet of Aspirin 75 mg (Control group), twice a day along with standard of care. Result: At the end of treatment, reduction was seen in the treatment group in score of 8-point ordinal scale, troponin, D-Dimer, Hs-CRP from baseline. There was a fall of 51.1% among control arm and 53.4% among treatment arm in 8-point ordinal score. The reduction in mean D-Dimer was 37% in control group and 38.1% in treatment group. The mean reduction in CT severity score in control group was 3.65 and in treatment group was 4.82, and the difference between the two groups was statistically significant (P value = 0.018). Conclusion: It was evident from CT scan scores that the treatment group has shown significant improvement in the reduction of inflammation and other COVID-19 symptoms as compared to the control group. The fall in Ferritin, Hs-CRP and D-Dimer level after treatment were indicative of improvement in internal inflammatory response of body in COVID-19 disease. As increased troponin levels indicate some degree of heart damage, the fall in troponin levels indicated that test treatment improved heart health in COVID-19 patients.

Molecular Characterization of the Functional Genes Associated with Silk Assembly, Transport, and Protection in the Silk Glands of Popular Multivoltine Breeds of Silkworm Bombyx mori. L.

Bombyx mori is an agriculturally important insect used extensively for silk production. India, especially the eastern regions, is mostly dependent on the multivoltine breeds of silkworm Bombyx mori and their hybrids/crossbreeds. The multivoltine breeds are indigenous and superior in survival and hardiness but are relatively inferior in terms of qualitative traits, typically the silk quality. Therefore, it is highly relevant to understand the mechanism of silk production in the multivoltine breeds to decipher the reasons for the inferior quality of silk produced by the multivoltine breeds and thus gain leads to improve the quality of silk production in multivoltine breeds. With this background, study was carried to identify differential expression of the major genes associated with silk proteins in the silk gland region of the popular multivoltine breeds. Our results indicated that although fib-L, fib-H, Sericins, and P25 are the major genes associated with silk filament, a few other genes associated with silk assembly, transport, and protection in the silk glands are the ones that largely contribute towards efficient silk production. The differential expression of these genes had a major effect on the movement of silk proteins within the silk gland and the efficiency of silk production as well. The Pearson correlation revealed a positive correlation amongst the genes dealt with in this study, indicating that the concurrent increase in expression of both the types of genes in the silk glands, significantly improves the silk production.

Efficacy and safety of 400 mg efavirenz versus standard 600 mg dose when taken with tenofovir and lamivudine combination in Indian adult patients with HIV-1 infection: An open-label, interventional, randomized, non-inferiority trial.

BACKGROUND: To evaluate the non-inferiority of low dose efavirenz (400 mg) to standard dose efavirenz (600 mg), when taken in combination with tenofovir and lamivudine in Indian patients with HIV-1 infection. METHODS: An open-label, interventional phase IV study with blinded assessment was conducted across 17 sites in India. HIV-1-infected antiretroviral therapy-naive adult patients (≥18 years of age) with a plasma HIV-1 viral load of at least 1000 copies per mL were randomized to receive either tenofovir/lamivudine/efavirenz (TLE) 400 or TLE 600. The primary endpoint was the difference in the proportion of patients achieving < 200 copies per mL at the end of 24 weeks. RESULTS: A total of 265 patients were enrolled and were randomized in 1:1 ratio to TLE 400 group (130 patients) and TLE 600 group (135 patients). At week 24, the proportion of patients with a viral load of less than 200 copies per mL was 80.70% for TLE 400 and 78.95% for TLE 600 (difference 1.75%, 90% confidence interval: -7.01, 10.49) which was within the predefined margin of -10% (90% confidence interval). Significantly lower study drug-related adverse events were observed in TLE 400 group compared to TLE 600 group (52.30%, n = 68 vs 64.92%, n = 87; P = .037). The treatment discontinuation percentage was marginally higher by 2.08% in TLE 600 group. CONCLUSION: The fixed-dose combination of TLE 400 is non-inferior to TLE 600 in terms of viral suppression and has an improved safety profile over 24 weeks in adult Indian patients with HIV-1 infection.

Methanol extraction revealed anticancer compounds Quinic Acid, 2(5H)­Furanone and Phytol in Andrographis paniculata.

Andrographis paniculata (Ap) has been a part of traditional medicine for its anti-inflammatory effects, treatment of snake bites and liver abnormalities. Several investigations have revealed its bioactive components to be andrographolides. The methanolic extracts of leaves from Ap were characterized, the non-andrographolides were identified and screened for anti-proliferative activity. The extracts showed significant toxicity against numerous cancer cells including HeLa, MCF7, BT549, 293 and A549 cells. Anti-proliferative activity and effect on cancer cell invasion (metastatic potential) and cell migration were examined. The extracts revealed significant inhibition of the ability of HeLa cells in repairing the gap created by a vertical wound made on a confluent cell monolayer. Similarly, a 40% reduction in cell migration was observed in presence of the extracts. Significant anti-angiogenic activity in terms of reduced blood capillary formation was observed on the Chorioallantoic membranes of embryonated hen eggs co-inoculated with HeLa cells and the extracts. Analysis of HeLa cells treated with the extracts using flow cytometry indicated the arrest of cell cycle progression at the G2/M phase. Variation in the Bax/Bcl-2 ratio and elevated caspase-3 levels by immunoblotting confirmed cell death induction via the apoptotic pathway. Investigation of the extracts by gas chromatography-mass spectrometry displayed the predominant components to be 2(5H)-Furanone (14.73%), Quinic acid (17.32%), and Phytol (11.43%). These components have been previously known to have anticancer activity, while being studied individually in other plants. This is the first study, to the best of our knowledge, on the anti-proliferative and anti-angiogenic activity of the non-andrographolide components from Ap.

A Phase IV Study on Safety, Tolerability and Efficacy of Dolutegravir, Lamivudine, and Tenofovir Disoproxil Fumarate in Treatment Naïve Adult Indian Patients Living with HIV-1.

Purpose: WHO recommends dolutegravir (DTG) based regimens as first-line treatment for HIV-1 infection. However, few studies have been conducted in Indian population. Hence, our study evaluated the safety, tolerability, and efficacy of DTG 50 mg with Tenofovir and Lamivudine (300/300mg) fixed dose combination in treatment naïve adult Indian patients. Methods: This was an open label, multicenter, prospective, interventional, phase IV study conducted across 14 sites between February 2019 and July 2020. 24 weeks was the treatment duration for each subject. The primary end point was to assess the incidence of adverse events (AEs) and secondary end points were to assess the proportion of patients achieving plasma HIV-1 RNA levels <50 copies/mL at week 24 and change in CD4+ cell count from the baseline. Safety analysis was conducted using Safety Analysis Set and efficacy analysis was carried out using Full Analysis Set and Per protocol set. Results: A total of 288 patients were screened; 250 were enrolled; and 229 completed the study. 389 AEs were reported from 58% of patients. Of these, 61 were related to study treatment. One event of decreased creatinine clearance led to study discontinuation. One serious event of pyrexia was reported, which was unrelated to the study drug. The most common AEs were headache (18%), pyrexia (14%), vomiting (6.4%) and upper respiratory tract infections (6%). No deaths were reported. At week 24, 86.8% of the patients achieved plasma HIV-1 RNA levels <50 copies/mL and the mean CD4 cell count increased from 350.2 (SD, 239.73) at baseline to 494.6 (SD, 261.40) with an average increase of 143.2 (SD, 226.14) cells. Conclusion: This study demonstrated the safety and efficacy of DTG based regimen in treatment naïve HIV-1 patients in Indian population and support use of DTG as first-line treatment regimen.

Evolution and co-evolution: insights into the divergence of plant heat shock factor genes.

The Heat Shock Factor (Hsf) genes are widely distributed across the plant kingdom regulating the plant response to various abiotic stresses. In addition to natural selection, breeding and accelerated selection changed the structure and function of Hsf genes. 1076 Hsf genes from 30 genera from primitive algae to the most advanced plant species and major crop plants were used for phylogenetic analysis. The interspecific divergence was studied with 11 members of genus Oryza while intraspecific divergence was studied with sesame pan-genome adapted to diverse ecological niches. B2 genes in eudicots and monocots originated separately while A1 gave rise to the recently evolved Class-C genes and land colonization happened with evolution of A1 genes. An increase in the number of lineages in the Oryza clade with the evolution of AA genome indicated independent domestication and positive selection was observed in > 53% of loci whereas the highly conserved homologues were under purifying selection. The paralogous genes under positive selection exhibited more domain changes for diversified function and increased fitness. A significant co-evolving cluster involving amino acids Phenylalanine, Lysine and Valine played crucial role in maintaining hydrophobic core along with highly conserved Tryptophan residues. A mutation of Glutamic acid to Glutamine was observed in A8 genes of Lamiales affecting protein solvency. Breeding resulted in accumulation of mutations reducing the hydrophobicity of proteins and a further reduction in protein aggregation. This study identify genome duplications, non-neutral selection and co-evolving residues as causing drastic changes in the conserved domain of Hsf proteins. Supplementary information: The online version contains supplementary material available at 10.1007/s12298-022-01183-7.

Gene fusions, micro-exons and splice variants define stress signaling by AP2/ERF and WRKY transcription factors in the sesame pan-genome.

Evolutionary dynamics of AP2/ERF and WRKY genes, the major components of defense response were studied extensively in the sesame pan-genome. Massive variation was observed for gene copy numbers, genome location, domain structure, exon-intron structure and protein parameters. In the pan-genome, 63% of AP2/ERF members were devoid of introns whereas >99% of WRKY genes contained multiple introns. AP2 subfamily was found to be micro-exon rich with the adjoining intronic sequences sharing sequence similarity to many stress-responsive and fatty acid metabolism genes. WRKY family included extensive multi-domain gene fusions where the additional domains significantly enhanced gene and exonic sizes as well as gene copy numbers. The fusion genes were found to have roles in acquired immunity, stress response, cell and membrane integrity as well as ROS signaling. The individual genomes shared extensive synteny and collinearity although ecological adaptation was evident among the Chinese and Indian accessions. Significant positive selection effects were noticed for both micro-exon and multi-domain genes. Splice variants with changes in acceptor, donor and branch sites were common and 6-7 splice variants were detected per gene. The study ascertained vital roles of lipid metabolism and chlorophyll biosynthesis in the defense response and stress signaling pathways. 60% of the studied genes localized in the nucleus while 20% preferred chloroplast. Unique cis-element distribution was noticed in the upstream promoter region with MYB and STRE in WRKY genes while MYC was present in the AP2/ERF genes. Intron-less genes exhibited great diversity in the promoter sequences wherein the predominance of dosage effect indicated variable gene expression levels. Mimicking the NBS-LRR genes, a chloroplast localized WRKY gene, Swetha_24868, with additional domains of chorismate mutase, cAMP and voltage-dependent potassium channel was found to act as a master regulator of defense signaling, triggering immunity and reducing ROS levels.

Effect of indirect ultrasonic activation of modified bioceramic materials on the bond strength and tubular penetration in root canals.

BACKGROUND: To maintain the integrity of the interface between root canal filling and radicular dentin an ideal endodontic biomaterial should have good adhesion. This study was aimed to evaluate the bond strength and tubular penetration of modified bioceramic materials by indirect ultrasonic activation. MATERIALS AND METHODS: In the present in vitro experimental study, 120 coronal root slices of 2 mm were prepared from mandibular premolars and randomly divided into six groups (n = 20) in accordance to placement techniques: Group I: Nano Biodentine-manual, Group II: CaCl2 modified ProRootMTA-manual (MM), Group III: Biodentine-manual, Group IV: Nano Biodentine: Ultrasonic, Group V: CaCl2 modified ProRootMTA-ultrasonic, and Group VI: Biodentine-ultrasonic (BDU). The samples were kept in humidifier for 4 days at 37°C and push out bond strength, sealer penetration were evaluated using an universal testing machine and confocal laser scanning microscope respectively. Data were subjected to statistical analysis using SPSS software by using One-way ANOVA for overall significance and Tukey's multiple post hoc test for intergroup comparison (P < 0.05). RESULTS: Highest push out bond strength and greater tubular penetration were observed with Group VI (BDU), while the lowest bond strength and tubular penetration were associated with Group II (MM). CONCLUSION: Within the limitations of current study it was observed that Biodentine with indirect ultrasonic activation has resulted in highest pushout bond strength among all the study groups.

Efficacy of green jackfruit flour as a medical nutrition therapy replacing rice or wheat in patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study.

BACKGROUND/OBJECTIVES: Medical nutrition therapy along with pharmacological interventions as a multidisciplinary approach is required to treat type 2 diabetes mellitus (T2DM). This study evaluated the efficacy of Jackfruit365™ green jackfruit flour as an integral part of daily meal in patients with T2DM. SUBJECTS/METHODS: This was a randomized, double-blind, placebo-controlled study conducted between May 2019 and February 2020. Patients of either sex aged ≥18 to ≤60 years with a diagnosis of T2DM for >1 year receiving oral antihyperglycemic agents were randomized (1:1) to receive either jackfruit flour 30 g/day (Group A) or placebo flour (Group B) (breakfast and dinner) daily for 12 weeks replacing an equal volume of rice or wheat flour. The primary endpoint was a mean change in glycosylated hemoglobin (HbA1c). Other endpoints were mean changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), lipid profile, and body weight. The independent t-test was used to compare changes between the groups. RESULTS: A total of 40 patients were enrolled (n = 20 each). A significantly higher reduction in HbA1c was observed in Group A compared to Group B from baseline to week 12 [-2.73 mmol/mol (-0.25%) vs. 0.22 mmol/mol (0.02%), p = 0.006]. The mean change in FPG and PPG was significantly higher in Group A than that of Group B (p = 0.043 and p = 0.001). The continuous glucose monitoring showed decreasing mean blood glucose in 7 days of administration of jackfruit flour meal. CONCLUSION: Patients from Group A had a significantly higher reduction in HbA1c, FPG, and PPG than Group B demonstrating the efficacy of jackfruit flour in glycemic control as medical nutrition therapy replacing an equal volume of rice or wheat flour in daily meal. CLINICAL TRIAL REGISTRY: CTRI/2019/05/019417.

Evaluation of the Efficacy and Safety of Azilsartan in Adult Patients with Essential Hypertension: A Randomized, Phase-III Clinical Study in India.

BACKGROUND: Globally, women and men over the age of 25 years suffer from hypertension, the need for new treatment strategies to treat hypertension is due to the multi-faceted nature of the disease. Lack of optimal blood pressure control can lead to multiple complications. Therefore, this phase 3 study was conducted to assess the efficacy, safety and tolerability of potential product azilsartan hydrochloride for reduction in blood pressure in Indian patients with essential hypertension. METHODS: This was a prospective, multicentre, randomized, comparative, parallel study of 303 participants over six weeks of treatment period with either azilsartan 40 mg or azilsartan 80 mg or telmisartan 40 mg in adult patients with essential hypertension. The primary endpoint was the change in mean trough sitting clinic systolic blood pressure (scSBP) from baseline to week 6. The secondary endpoints were the change in mean trough sitting clinic diastolic blood pressure (scDBP) from baseline and change in the 24-hour mean ambulatory systolic blood pressure (SBP)and diastolic blood pressure (DBP) from baseline. RESULTS: The change in mean trough scSBP from baseline to week 6 was -27.2 ± 9.99, -28.2 ± 10.06 and -26.7 ± 9.72 (Per Patient (PP) Population) and -27.2 ± 9.93, -28.3 ± 10.01 and -26.7 ± 9.67 (Intent to Treat (ITT) Population) in the azilsartan 40mg, 80mg and telmisartan 40mg groups respectively. The lower limit of 95% CI of difference in change in mean systolic blood pressure was -2.35(Azilsartan 40mg) and 1.32 (Azilsartan 80mg) is less than the non-inferiority margin (i.e. 2.67). The change in mean trough scDBP from baseline to week 6 was -13.1 ± 8.46, -12.9 ± 7.20, and -13.0 ± 7.96 (PP) and -13.1 ± 8.42, -12.9 ± 7.16 and -13.0 ± 7.92 (ITT) in Azilsartna 40 mg, Azilsartan 80 mg and Telmisartan 40 mg respectively. The reduction in trough scDBP in Azilsartan 40 mg (p=0.9461: PP; p=0.9330: ITT) and Azilsartan 80 mg (p=0.9090: PP; p=0.9158: ITT) was not statistically significant compared to Telmisartan 40 mg. The difference in fall in the trough scSBP, scDBP and ambulatory SBP and DBP was similar between the groups from baseline to week 6 (P >0.05). Headache and dizziness were the most frequent treatmentrelated treatment-emergent adverse events. CONCLUSION: Azilsartan is an effective blood pressure lowering drug and well tolerated and was non- inferior to telmisartan in its safety and efficacy.

The Histopathology of Oral Cancer Pain in a Mouse Model and a Human Cohort.

Oral cancer patients often have severe, chronic, and mechanically induced pain at the site of the primary cancer. Oral cancer pain is initiated and maintained in the cancer microenvironment and attributed to release of mediators that sensitize primary sensory nerves. This study was designed to investigate the histopathology associated with painful oral cancers in a preclinical model. The relationship of pain scores with pathologic variables was also investigated in a cohort of 72 oral cancer patients. Wild-type mice were exposed to the carcinogen, 4-nitroquinoline 1-oxide (4NQO). Nociceptive (pain) behavior was measured with the dolognawmeter, an operant device and assay for measuring functional and mechanical allodynia. Lesions developed on the tongues and esophagi of the 4NQO-treated animals and included hyperkeratoses, papillomas, dysplasias, and cancers. Papillomas included lesions with benign and dysplastic pathological features. Two histologic subtypes of squamous cell carcinomas (SCCs) were identified-SCCs with exophytic and invasive components associated with papillary lesions (pSCCs) and invasive SCCs without exophytic histology (iSCCs). Only the pSCC subtype of tongue cancer was associated with nociceptive behavior. Increased tumor size was associated with greater nociceptive behavior in the mouse model and more pain experienced by oral cancer patients. In addition, depth of invasion was associated with patient-reported pain. The pSCC histology identifies 4NQO-induced tongue cancers that are expected to be enriched for expression and release of nociceptive mediators.

Targeting genes involved in nucleopolyhedrovirus DNA multiplication through RNA interference technology to induce resistance against the virus in silkworms.

RNA interference (RNAi) has become an efficient tool for inducing resistance to viruses in many organisms. In this study, Escherichia coli cells were engineered to produce stable double-stranded RNA (dsRNA) against the nucleopolyhedrosis virus to elicit RNAi in silkworms. The immediate-early-1 (ie-1) and late expression factor-1 (lef-1) genes of the Bombyx mori nucleopolyhedrovirus (BmNPV) involved in viral DNA multiplication were cloned in the plasmid L4440 under the influence of the double T7 promoter and transformed to E. coli HT115 DE3 host cells. On induction with isopropyl ß-D-thiogalactopyranoside, these cells efficiently produced dsRNA of the cloned genes. The B. mori larvae were fed with 50 µL of E. coli cells expressing ie-1 and lef-1 dsRNAs (each approximately 25 µg) to elicit RNAi. The semi-quantitative and quantitative PCR analysis of RNA from the midgut of the dsRNA-fed larvae revealed a significant reduction in the expression of the target genes involved in BmNPV multiplication, which restricted virus copy numbers to 100 compared with 1.9 × 105 in the infected controls. Furthermore, the dsRNA-fed infected larvae showed > 50% increased survivability compared with the infected controls. The study revealed the successful use of bacteria as vectors for efficiently delivering dsRNA to elicit RNAi against BmNPV in silkworms.

Effect of 17% ethylenediaminetetraacetic acid and 0.2% chitosan on pushout bond strength of biodentine and ProRoot mineral trioxide aggregate: An in vitro study.

AIM: The purpose of this study was to evaluate the effect of 17% ethylenediaminetetraacetic acid (EDTA) and 0.2% chitosan on pushout bond strength of biodentine and ProRoot mineral trioxide aggregate (MTA). MATERIALS AND METHODS: Midroot dentin of single-rooted human canine teeth were sectioned into 2-mm-thick slices horizontally (n = 60). The canal space of each dentin slice was enlarged with a 1.3-mm-diameter diamond bur. The samples were divided into two groups (n = 30) based on the type of perforation repair material placed, i.e., Biodentine and ProRoot MTA. The samples were wrapped in wet gauge for 10 min, and based on the type of chelating agent used for removal of smear layer, each group is further divided into three subgroups (n = 10), to be immersed into saline (control), 17% EDTA and 0.2% chitosan for 30 min, and a wet cotton pellet was placed over each test material. After 48 h of incubation, the dislodgement resistance of the samples was measured using a universal testing machine. STATISTICAL ANALYSIS: Data were analyzed using one-way analysis of variance and post hoc Tukey tests. The level of statistical significance was set at 0.05. RESULTS: Biodentine showed significantly higher pushout bond strength than ProRoot MTA. Biodentine and ProRoot MTA lost strength when exposed to 0.2% chitosan. CONCLUSION: Biodentine showed considerable performance as a perforation repair material than ProRoot MTA even after being exposed to various endodontic chelating agents.