Network pharmacology-based approach to investigate the molecular targets and molecular mechanisms of Rosmarinus officinalis L. for treating aging-related disorders.

Aging, a natural biological process, presents challenges in maintaining physiological well-being and is associated with increased vulnerability to diseases. Addressing aging mechanisms is crucial for developing effective preventive and therapeutic strategies against age-related ailments. Rosmarinus officinalis L. is a medicinal herb widely used in traditional medicine, containing diverse bioactive compounds that have been studied for their antioxidant and anti-inflammatory properties, which are associated with potential health benefits. Using network pharmacology, this study investigates the anti-aging function and underlying mechanisms of R. officinalis. Through network pharmacology analysis, the top 10 hub genes were identified, including TNF, CTNNB1, JUN, MTOR, SIRT1, and others associated with the anti-aging effects. This analysis revealed a comprehensive network of interactions, providing a holistic perspective on the multi-target mechanism underlying Rosemary's anti-aging properties. GO and KEGG pathway enrichment analysis revealed the relevant biological processes, molecular functions, and cellular components involved in treating aging-related conditions. KEGG pathway analysis shows that anti-aging targets of R. officinalis involved endocrine resistance, pathways in cancer, and relaxin signaling pathways, among others, indicating multifaceted mechanisms. Genes like MAPK1, MMP9, and JUN emerged as significant players. These findings enhance our understanding of R. officinalis's potential in mitigating aging-related disorders through multi-target effects on various biological processes and pathways. Such approaches may reduce the risk of failure in single-target and symptom-based drug discovery and therapy.

Label-free visualization of unfolding and crosslinking mediated protein aggregation in nonenzymatically glycated proteins.

Nonenzymatic glycation (NEG) unfolds and crosslinks proteins, resulting in aggregation. Label-free evaluation of such structural changes, without disturbing molecular integrity, would be beneficial for understanding the fundamental mechanisms of protein aggregation. The current study demonstrates the assessment of NEG-induced protein aggregation by combining autofluorescence (AF) spectroscopy and imaging. The methylglyoxal (MG) induced protein unfolding and the formation of cross-linking advanced glycation end-products (AGEs) leading to aggregation were evaluated using deep-UV-induced-autofluorescence (dUV-AF) spectroscopy in proteins with distinct structural characteristics. Since the AGEs formed on proteins are fluorescent, the study demonstrated the possibility of autofluorescence imaging of NEG-induced protein aggregates. Autofluorescence spectroscopy can potentially reveal molecular alterations such as protein unfolding and cross-linking. In contrast, AGE-based autofluorescence imaging offers a means to visually explore the structural arrangement of aggregates, regardless of whether they are amyloid or non-amyloid in nature.

Endophytic Fungi: Cellular factories of novel medicinal chemistries.

Inflammation and associated disorders have been a major contributing factor to mortality worldwide. The augmented mortality rate and emerging resistance against the approved therapeutics necessitate the discovery of novel chemistries destined for multiple clinical settings. Cellular factories including endophytic fungi have been tapped for chemical diversity with therapeutic potential. The emerging evidence has suggested the potential of bioactive compounds isolated from the endophytic fungi as putative agents to combat inflammation-associated disorders. The review summarizesand assists the readers in comprehending the structural and functional aspects of the medicinal chemistries identified from endophytic fungi as anticancer, antiobesity, antigout, and immunomodulatory agents.

Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

Indian Consensus on the Role and Position of Angiotensin Receptor-neprilysin Inhibitors in the Management of Heart Failure.

The incidence of heart failure (HF) in India is estimated to be 0.5-1.7 cases per 1,000 people per year, and approximately 4,92,000-1.8 million new cases are detected every year. Despite the high rate of mortality associated with HF, most patients do not receive maximal guideline-directed medical therapy (GDMT). Current guidelines advocate early multidrug combination therapy with four classes of drugs, namely, beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium-glucose transport protein 2 inhibitors (SGLT-2is), particularly in patients with heart failure with reduced ejection fraction (HFrEF). ARNIs reduce cardiac morbidity and mortality in patients with HFrEF. However, recent data indicated that only 4.8% of patients with HFrEF receive ARNI in India. Hence, at a national consensus on HF meeting, cardiology experts from India formulated a national consensus on the use of ARNI in HF based on current evidence and guidelines. The consensus states that ARNI should be used early in HF, particularly in de novo patients with HFrEF, and those with acute decompensated heart failure (ADHF), irrespective of the presence of low systolic blood pressure (SBP) or diabetes. Moreover, those with HFrEF on renin-angiotensin-aldosterone system (RAAS) inhibitors should be switched to ARNI to reduce the risk of repeated hospitalization for HF, worsening HF, and cardiac death, and to improve the quality of life (QoL). Starting ARNI during the first hospitalization is preferable, and it is safe and effective across all doses. ARNIs can also be used for secondary benefits in patients with preserved ejection fraction [heart failure with preserved ejection fraction (HFpEF)] and HF with mildly reduced EF [heart failure with mildly reduced ejection fraction (HFmrEF)].

Consensus Statement from India on the Renal Benefits of ARNi, SGLT-2i, and Bisoprolol in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All these comorbidities are risk factors for renal impairment. HF and CKD are pathophysiologically intertwined, and the deterioration of one can worsen the prognosis of the other. There is a need for safe renal pharmacological therapies that target both CKD and HF and are also useful in hypertension and diabetes. Neurohormonal activation achieved through the activation of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and the natriuretic peptide system (NPS) is fundamental in the pathogenesis and progression of CKD and HF. Angiotensin receptor neprilysin inhibitor (ARNi), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and selective ß1-blocker (B1B) bisoprolol suppress this neurohormonal activation. They also have many other cardiorenal benefits across a wide range of CKD patients with or without concomitant HF, diabetes, or hypertension. This consensus statement from India explores the place of ARNi, SGLT-2i, and bisoprolol in the management of CKD patients with or without HF and other comorbidities.

Protocolized Regional Citrate Anticoagulation during Continuous Renal Replacement Therapy: A Single Center Experience.

Background: Regional citrate anticoagulation (RCA) has emerged as a treatment modality that reduces bleeding risk and filter clotting. With initial experience of using RCA with continuous renal replacement therapy (CRRT), we have formulated a working protocol based on published literature. Objective: The study aimed to evaluate the protocol for routine use of RCA during CRRT requiring anticoagulation and evaluation of filter life. Methodology: It is a single-center, open-label, prospective, non-randomized, non-interventional, single-arm, observational study conducted at a tertiary care hospital between September 2022 and July 2023. All adult patients with acute kidney injury (AKI) or hyperammonemia requiring CRRT and necessitating the use of anticoagulation were enrolled in the study. The study used Prisma Flex M100 AN 69 dialyzer on Prisma Flex (Baxter) CRRT machines during continuous venovenous hemodiafiltration (CVVHDF). The targeted CRRT dose in all the study patients was 25-30 mL/kg/hour. Based on the published literature, we have developed a working protocol (Appendix 1) for managing patients on CRRT using RCA. Results: A total of 159 patients were analyzed for the study. The median [interquartile range (IQR)] filter life using RCA was 30 (12-55) hours. Filter clotting was observed in 33.3% of patients. Citrate accumulation was present in 52.25% of patients, but no CRRT was discontinued as citrate accumulation resolved after following the corrective steps in the protocol. None of the patients had citrate toxicity. Chronic liver disease (CLD) (p ≤ 0.001) and those who were post-living donor liver transplant recipients (p = 0.004) had a statistically significant increase in citrate accumulation. Also, patients who had higher lactate at baseline (6 hours post-CRRT initiation), had a higher chance of citrate accumulation. Conclusion: Our RCA protocol provides a safe approach to regional anticoagulation during CRRT in critically ill patients. How to cite this article: Pachisia AV, Kumar GP, Harne R, Jagadeesh KN, Patel SJ, Pal D, et al. Protocolized Regional Citrate Anticoagulation during Continuous Renal Replacement Therapy: A Single Center Experience. Indian J Crit Care Med 2024;28(9):859-865.

The restriction of calcium influx in metaphase and post-metaphase stages of cell division revealed by imaging secondary ion mass spectrometry (SIMS).

A secondary ion mass spectrometry (SIMS)-based isotopic imaging technique of ion microscopy was used for observing calcium influx in single renal epithelial LLC-PK1 cells. The CAMECA IMS-3f SIMS instrument, used in the study, is capable of producing isotopic images of single cells at 500 nm spatial resolution. Due to the high-vacuum requirements of the instrument the cells were prepared cryogenically with a freeze-fracture method and frozen freeze-dried cells were used for SIMS analysis. The influx of calcium was imaged directly by exposure of cells to 44 Ca stable isotope in the extracellular buffer for 10 min. The 44 Ca influx was measured at mass 44 and the distribution of endogenous calcium at mass 40 (40 Ca) in the same cell. A direct comparison of interphase cells to cells undergoing division revealed that calcium influx is restricted in metaphase and post-metaphase stages of cell division. This restriction is lifted in late cytokinesis. The net influx of 44 Ca in 10 min was approximately half under calcium influx restriction in comparison to interphase cells. Under calcium influx restriction the 44 Ca concentration was the same between the mitotic chromosome and the cytoplasm. These observations indicate that the endoplasmic reticulum (ER) calcium uptake is compromised under calcium influx restriction in cells undergoing division.

Network pharmacology, molecular docking, and molecular dynamics simulation to elucidate the mechanism of anti-aging action of Tinospora cordifolia.

Scientific research has demonstrated that Tinospora cordifolia acts as an anti-aging agent in several experimental models, generating global interest in its underlying molecular mechanisms of this activity. The aim of the study was to identify the possible phytochemical compounds of T. cordifolia that might combat age-related illness through integrating network pharmacology, molecular docking techniques, and molecular dynamics (MD) study to explore their potential mechanisms of action. To carry out this study, several databases were used, including PubChem, KNApSAcK family database, PubMed, SwissADME, Molsoft, SwissTargetPrediction, GeneCards, and OMIM database. For network development and GO enrichment analysis KEGG, ShinyGo 0.77, and the STRING database were used. For better analysis, the networks were also constructed using Cytoscape 3.9.1. The Cytoscape network analyzer tool was used for data analysis, and molecular docking was done via Vina-GPU-2.0. The best compounds and AKT1 were finally subjected to MD simulation for 100 ns. The CytoHubba plugin of Cytoscape identified ten key targets, commonly called hub genes, including AKT1, GAPDH, and TP53, and so on. GO and KEGG pathway enrichment analysis revealed the relevant biological processes, cellular components, and molecular functions involved in treating aging-related disorders. KEGG pathway analysis involved neuroactive ligand-receptor interactions, lipid and atherosclerosis, and cAMP signaling. The docking of 100 T. cordifolia compounds with AKT1 demonstrated good binding affinity, particularly for Amritoside, Sitagliptin, Berberine, and Piperine. Finally, the relative stability of four-hit phytochemicals was validated by MD simulation, which may be the most crucial compound for anti-aging activity. In conclusion, this study used network pharmacology, molecular docking, and MD simulation to identify the compounds in T. cordifolia and proposed a potential mechanism for anti-aging activity. These results suggest future directions for the prevention and treatment of age-related diseases.

Development of Rice Straw-derived Biochar-Bentonite Composite and its Application for in situ Sequestration of Ammonium and Phosphate Ions in the Degraded Mine Soil.

Nutrient pollution has a diverse impact on the environment and human health. The presence of nutrients, such as ammonium and phosphate, is ubiquitous in the environment due to their extensive use in agricultural land and leaching through non-point sources. In this context, biochar-based composites could play an essential role in improving the soil's nutrient retention capacity. The present study aims to develop bentonite-biochar composites (BNT@BC 400 and 600) and utilize them as an ameliorating material in the coal mine degraded soil to reduce the leaching of ammonium and phosphate ions. The bentonite-biochar composite (BNT@BC 400 and 600) was synthesized using the pristine rice straw-derived biochar using the solvothermal method. The biochar was produced at two different pyrolytic temperatures, 400 °C and 600 °C, and denoted as BC 400 and 600, respectively. Hence, the bentonite-biochar composite was denoted as BNT@BC 400 and 600. The BNT@BC 400 and 600 were characterized using the elemental, proximate, SEM, XRD, and FTIR analysis. Subsequently, the BNT@BC composites were evaluated for the adsorptive removal of NH4+ and PO43- ions using batch adsorption and column leaching studies. In the soil columns, the BNT@BC 400 and 600 were mixed with the soil at two different application rates, viz. 1 and 2.5% (w/w). The leaching characteristics data were fitted using three different fixed-bed models to predict the maximum adsorption capacity of the amended soil columns and the dominant mechanism of adsorption. Results indicated that the BNT@BC 600 showed the maximum adsorption capacity of 33.77 and 64.23 mg g-1 for the adsorption of NH4+ and PO43- ions, respectively. The dominant adsorption mechanisms in the aqueous solution were the electrostatic attraction, complexation, ion exchange, and precipitation processes. In the soil columns, the sorption of NH4+ and PO43- ions was governed by diffusive mass transfer and electrostatic interaction. Findings of the study indicated that incorporating the BNT@BC composite in the soil can significantly reduce the leaching of the NH4+ and PO43- ions and increase the overall soil fertility.

Role of Bisoprolol in Heart Failure Management: A Consensus Statement from India.

In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective ß-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a ß-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.

Measurement of radon concentration in soil gas and radon exhalation rate from soil samples along and across the Main Central Thrust of Garhwal Himalaya, India.

The present study focuses on measuring radon concentrations in soil gas at various depths, radon exhalation rate (surface and mass) from soil samples, and gamma dose rate along and across the Main Central Thrust of Garhwal Himalaya, India. Radon concentration in soil gas, surface, and mass exhalation rates was measured using a portable SMART radon monitor (RnDuo). Furthermore, the gamma dose rate was measured using a pocket radiation monitor. The soil gas radon concentration varied from 15 ± 4 to 579 ± 82 Bq m-3 at a depth of 25 cm, 10 ± 2 to 533 ± 75 Bq m-3 at a depth of 30 cm, and 9 ± 1 to 680 ± 95 Bq m-3 at a depth of 35 cm. The surface and mass exhalation rates were found 3 ± 0.7 to 98 ± 3 Bq m-2 h-1 (with AM ± SD = 36 ± 28 Bq m-2 h-1) and 1 ± 0.2 to 95 ± 2 mBq kg-1 h-1 (with AM ± SD = 30 ± 22 mBq kg-1 h-1), respectively. The gamma dose rate for the present study area varies from 0.11 ± 0.05 to 0.28 ± 0.05 µSv h-1 with a mean value of 0.17 ± 0.05 µSv h-1. The correlation analysis between the exhalation rates (mass and surface) and radon concentration of soil gas at various depths was carried out in the current study.

Comparison of recovery profiles in target-controlled infusions (TCI) versus manually controlled infusions for total intravenous anesthesia (TIVA) in laparoscopic surgeries. A randomized controlled trial.

Background and Aims: Considerable importance has been attached to early recovery and discharge readiness after surgeries. Many centers use total intravenous anesthesia (TIVA) as their anesthesia technique of choice. Target-controlled infusions (TCI) have been proposed as a method to precisely deliver continuous infusions of propofol and opioids as compared to the traditionally used manual-controlled infusion (MCI) methods. However, TCI has also been shown to result in the administration of larger doses of propofol which could cause delayed emergence and recovery from anesthesia. Studies involving TCI have focused mainly on its effects on anesthesia induction but not much literature is available on recovery profiles of patients on TCI. This study was designed to compare the effect of conventionally used MCI methods versus the target-controlled infusion (TCI) method of administering TIVA on recovery characteristics in patients undergoing laparoscopic surgery. Material and Methods: This was a prospective randomized interventional study on 54 patients. Our primary objective was to compare the rates of recovery from anesthesia as judged by four parameters. Time to return of spontaneous ventilation, time to respond to verbal commands, time to extubation, and time to shift patient out of the operating room after stoppage of propofol infusion. As secondary objectives, intraoperative average bispectral index (BIS) values and total anesthetic drugs (propofol and fentanyl) consumption were also compared. Results: We noted that for laparoscopic surgeries lasting less than 4 hours, both MCI and TCI techniques of TIVA have comparable rates of recovery after the stoppage of propofol infusion. Total consumption of propofol and fentanyl was also similar; however, with the use of the TCI method of TIVA, better depth of anesthesia as evidenced by lower average BIS levels was noted. Conclusion: Recovery rates after TIVA using a target-controlled infusion (TCI) system are similar to BIS-guided MCIs in patients undergoing laparoscopic surgery lasting less than 4 hours. TCI resulted in better depths of anesthesia though per kg/min consumption of propofol was found to be more.

Computational investigation of drug bank compounds against 3C-like protease (3CLpro) of SARS-CoV-2 using deep learning and molecular dynamics simulation.

Blocking the main replicating enzyme, 3 Chymotrypsin-like protease (3CLpro) is the most promising drug development strategy against the SARS-CoV-2 virus, responsible for the current COVID-19 pandemic. In the present work, 9101 drugs obtained from the drug bank database were screened against SARS-CoV-2 3CLpro prosing deep learning, molecular docking, and molecular dynamics simulation techniques. In the initial stage, 500 drug-screened by deep learning regression model and subjected to molecular docking that resulted in 10 screened compounds with strong binding affinity. Further, five compounds were checked for their binding potential by analyzing molecular dynamics simulation for 100 ns at 300 K. In the final stage, two compounds {4-[(2s,4e)-2-(1,3-Benzothiazol-2-Yl)-2-(1h-1,2,3-Benzotriazol-1-Yl)-5-Phenylpent-4-Enyl]Phenyl}(Difluoro)Methylphosphonic Acid and 1-(3-(2,4-dimethylthiazol-5-yl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-yl)-3-(4-methylpiperazin-1-yl)urea were screened as potential hits by analyzing several parameters like RMSD, Rg, RMSF, MMPBSA, and SASA. Thus, our study suggests two potential drugs that can be tested in the experimental conditions to evaluate the efficacy against SARS-CoV-2. Further, such drugs could be modified to develop more potent drugs against COVID-19.

Integrated Machine Learning and Chemoinformatics-Based Screening of Mycotic Compounds against Kinesin Spindle ProteinEg5 for Lung Cancer Therapy.

Among the various types of cancer, lung cancer is the second most-diagnosed cancer worldwide. The kinesin spindle protein, Eg5, is a vital protein behind bipolar mitotic spindle establishment and maintenance during mitosis. Eg5 has been reported to contribute to cancer cell migration and angiogenesis impairment and has no role in resting, non-dividing cells. Thus, it could be considered as a vital target against several cancers, such as renal cancer, lung cancer, urothelial carcinoma, prostate cancer, squamous cell carcinoma, etc. In recent years, fungal secondary metabolites from the Indian Himalayan Region (IHR) have been identified as an important lead source in the drug development pipeline. Therefore, the present study aims to identify potential mycotic secondary metabolites against the Eg5 protein by applying integrated machine learning, chemoinformatics based in silico-screening methods and molecular dynamic simulation targeting lung cancer. Initially, a library of 1830 mycotic secondary metabolites was screened by a predictive machine-learning model developed based on the random forest algorithm with high sensitivity (1) and an ROC area of 0.99. Further, 319 out of 1830 compounds screened with active potential by the model were evaluated for their drug-likeness properties by applying four filters simultaneously, viz., Lipinski's rule, CMC-50 like rule, Veber rule, and Ghose filter. A total of 13 compounds passed from all the above filters were considered for molecular docking, functional group analysis, and cell line cytotoxicity prediction. Finally, four hit mycotic secondary metabolites found in fungi from the IHR were screened viz., (-)-Cochlactone-A, Phelligridin C, Sterenin E, and Cyathusal A. All compounds have efficient binding potential with Eg5, containing functional groups like aromatic rings, rings, carboxylic acid esters, and carbonyl and with cell line cytotoxicity against lung cancer cell lines, namely, MCF-7, NCI-H226, NCI-H522, A549, and NCI H187. Further, the molecular dynamics simulation study confirms the docked complex rigidity and stability by exploring root mean square deviations, root mean square fluctuations, and radius of gyration analysis from 100 ns simulation trajectories. The screened compounds could be used further to develop effective drugs against lung and other types of cancer.

Assessment of Risk of Malignancy of Fine-needle Aspiration Cytology in Salivary Gland Lesions Using the Milan System for Reporting Salivary Gland Cytopathology Categorization: A Systematic Review and Meta-analysis.

BACKGROUND: Fine-needle aspiration cytology (FNAC) of the salivary gland is crucial in the identification of salivary gland lesions, but the variation in morphological pattern and the overlap of morphological traits can result in erroneous interpretation and affect treatment, making FNAC of the salivary gland problematic. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was created to address these problems. OBJECTIVES: To ascertain whether the FNAC method using MSRSGC was reliable in predicting the risk of malignancy (ROM) in each category of salivary gland lesions. MATERIALS AND METHODS: The databases PubMed-MEDLINE, Web of Science, Cochrane, Scopus, and Google Scholar were all searched using pertinent keywords, reference searches, and citation searches. A fixed effect model was used to determine the pooled proportion with a 95% confidence interval (CI). All statistical analyses were performed using Meta Disc and R version 4.0.2 (R Foundation for Statistical Computing). RESULTS: After reviewing the submissions' abstracts and titles, 58 documents that satisfied the necessary inclusion and exclusion criteria were ultimately selected. A total of 19,652 samples from 19,408 individuals was analyzed, out of which 9,958 samples were available for histopathological follow-up. The pooled ROM for category I was 10%, category II was 5%, category III was 28%, category IV A was 2%, Category IV B was 34%, category V was 91%, and category VI was 99%. CONCLUSION: Milan System for Reporting Salivary Gland Cytopathology is useful for risk stratification and quality control, confirming its validity and diagnostic utility. Widespread use of MSRSGC would improve the accuracy of salivary gland cytology and lead to better patient care and improved treatment strategies. The results of this study are in consonance with reported values as per MSRSGC except for category V. CLINICAL SIGNIFICANCE: The MSRSGC which was first reported in 2018 is a very useful tool for proper stratification of ROM in salivary gland FNAC. This study allowed us to validate the ROM values in different categories as reported in MSRSGC.

Separation Effect and Perception of Pain and Discomfort from Kesling and Elastomeric Orthodontic Separators: An In Vivo Study.

AIM: To scrutinize Kesling and elastomeric orthodontic separators, focusing on the separating effect as well as patients' perception of pain together with discomfort. MATERIALS AND METHODS: The separators tested were elastomeric as well as Kesling separators. Thirty subjects, scheduled for treatment having a fixed orthodontic appliance, were categorized into two groups. In group I subjects, elastomeric separators were placed, whereas in group II subjects, Kesling separators were placed. After 3 days, the extent of separation was recorded with a leaf gauge. A questionnaire of eight questions and visual analog scale were used to note the patient perceptions of pain and discomfort. RESULTS: The mean separation formed by elastomeric and Kesling separator was 0.0457 and 0.0437 mm, respectively, of which elastomeric separator had made highest separation than the other separator used for the generation of separation at day 1 whereas the mean separation created by the elastomeric and Kesling separator at day 2 was 0.2327 mm and 0.1903 mm, respectively. 46.7% of patients on day 1, and on day 2, 56.7% of patients reported discomfort but not pain, while 73.3% of patients on day 3 reported discomfort but not pain from both types of separator. On day 1, 6.7% of patients, 13.3% on day 2, and 6.7% again on day 3 reported feeling pressure but no pain or discomfort. CONCLUSION: Elastomeric separators exhibited the highest separation compared to Kesling used for the separation, at all three days. The Kesling separator was a separator of choice in cases where the interproximal contact was tight. CLINICAL SIGNIFICANCE: Discomfort and pain due to separator will be minimized by reducing the duration of separator placement. Hence treatment acceptability will be more. There is no significant difference found in separation by increasing the day.

Exploring photoacoustic spectroscopy-based machine learning together with metabolomics to assess breast tumor progression in a xenograft model ex vivo.

In the current study, a breast tumor xenograft was established in athymic nude mice by subcutaneous injection of the MCF-7 cell line and assessed the tumor progression by photoacoustic spectroscopy combined with machine learning tools. The advancement of breast tumors in nude mice was validated by tumor volume kinetics and histopathology and corresponding image analysis by TissueQuant software compared to controls. The ex vivo tumors in progressive conditions belonging to time points, day 5th, 10th, 15th & 20th, were excited with 281 nm pulsed laser light and recorded the corresponding photoacoustic spectra in time domain. The spectra were then pre-processed, augmented for a 10-fold increase in the data strength, and subjected to wavelet packet transformation for feature extraction and selection using MATLAB software. In the present study, the top 10 features from all the time point groups under study were selected based on their prediction ranking values using the mRMR algorithm. The chosen features of all the time-point groups were then subjected to multi-class Support Vector Machine (SVM) algorithms for learning and classifying into respective time point groups under study. The analysis demonstrated accuracy values of 95.2%, 99.5%, and 80.3% with SVM- Radial Basis Function (SVM-RBF), SVM-Polynomial & SVM-Linear, respectively. The serum metabolomic levels during tumor progression complemented photoacoustic patterns of tumor progression, depicting breast cancer pathophysiology.

Consensus document: management of heart failure in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a known predisposing factor for heart failure (HF). The growing burden of these two conditions and their impact on health of the individual and on society in general needs urgent attention from the health care professionals. Availability of multiple treatment choices for managing T2DM and HF may make therapeutic decisions more complex for clinicians. Recent cardiovascular outcome trials of antidiabetic drugs have added very robust evidence to effectively manage subjects with this dual condition. This consensus statement provides the prevalence trends and the impact of this dual burden on patients. In addition, it concisely narrates the types of HF, the different treatment algorithms, and recommendations for physicians to comprehensively manage such patients.

Small and large scale plasmonically enhanced luminescent solar concentrator for photovoltaic applications: modelling, optimisation and sensitivity analysis.

Hybrid 3D Finite difference time domain-Monte Carlo ray tracing (FDTD-MCRT) algorithm has been developed to model and optimise small and large scale plasmonically-enhanced luminescent solar concentrator (pLSC) devices for photovoltaic (PV) applications. The configuration parameters (for example, dimensions, shape, and optical properties of metal nanoparticles, luminescent species, and host material) were used to characterise the probability of optical energy transfer and loss processes, as well as reflection, refraction, absorption, emission enhancement, and total internal reflection (TIR) in the pLSC. The algorithm was validated through modelling of various doping concentrations of CdSe/ZnS quantum dots (QD) and gold nano spheres (Au NS) where ∼50% enhancement in optical conversion efficiency (OCE) was observed for a plasmonic composite of 2 ppm Au NS and 0.008 wt. % QD.