Physiochemical characterization of sodium doped zinc oxide nano powder for antimicrobial applications.

Zinc oxide (ZnO) is one of the semiconductor materials with unique antimicrobial properties towards various microorganisms. In this article, pure and Na doped ZnO nanopowders were synthesized by easiest and cost-effective co-precipitation process. X-ray diffraction (XRD),Fourier transform infrared spectroscopy(FT-IR), ultraviolet - visible (UV - Vis) spectroscopy, scanning electron microscopy(SEM), and Energy dispersive X-ray analysis (EDAX) techniques were used to characterize the particle size, surface morphology and chemical composition of prepared materials. The XRD analysis revealed that the samples exhibiting hexagonal wurtzite crystal structure with high crystallinity and the average crystallite size values increased from 23.51 to 28.118 nm. The UV - Vis spectroscopy results exposed that the bandgap energy (Eg) of the samples with the values in the range of 3.068-3.301 eV. The SEM micrographs showed that the morphology of the of synthesized particles are hexagonal and spherical in nanometric size. The EDX spectra confirmed the elemental composition of Na, Zn and O in the crystal lattice and FTIR spectroscopic data proved the formation of functional groups and the presence of chemical bonding at the ZnO interface.Antibacterial activity of pure and Na doped Zinc oxide nanoparticles against Gram-negative pathogenssuch as Escherichia coli, Pseudomonas aeruginosa & Klebsiella pneumoniae and Gram-positive pathogens such as Staphylococcus aureus reveal that the zone of inhibition increases with increasing Na concentration. The antifungal activity against Aspergillus and Candida was investigated.These results demonstrated that the pure and Na doped ZnO samples exhibit enhanced antibacterial and antifungal activity with increasing particle sizein presence of visible light and they could be used as good antibacterial as well as antifungal agents.

Engineered upconversion nanocarriers for synergistic breast cancer imaging and therapy: Current state of art.

Breast cancer is the most common type of cancer in women and is the second leading cause of cancer-related deaths worldwide. Early diagnosis and effective therapeutic interventions are critical determinants that can improve survival and quality of life in breast cancer patients. Nanotheranostics are emerging interventions that offer the dual benefit of in vivo diagnosis and therapeutics through a single nano-sized carrier. Rare earth metal-doped upconversion nanoparticles (UCNPs) with their ability to convert near-infrared light to visible light or UV light in vivo settings have gained special attraction due to their unique luminescence and tumor-targeting properties. In this review, we have discussed applications of UCNPs in drug and gene delivery, photothermal therapy (PTT), photodynamic therapy (PDT) and tumor targeting in breast cancer. Further, present challenges and future opportunities for UCNPs in breast cancer treatment have also been mentioned.

Dual modal spectroscopic tissue scanner for colorectal cancer diagnosis.

BACKGROUND: Margin status is an important prognostic factor for treating colorectal cancer. This study aimed to investigate the usefulness of a multimodal spectroscopic tissue scanner for real-time cancer diagnosis without tissue staining. PATIENTS AND METHODS: Diffuse reflectance spectra (DRS) and fluorescence spectra (FS) of < 1-mm-sized paired cancer and normal mucosa tissue were acquired using custom-built spectroscopic tissue scanners. For FS, we analyzed wavelengths and intensities at peaks and highest intensities near (± 1.25 nm) the known fluorescence spectral peaks of collagen (380 nm), reduced nicotinamide adenine dinucleotide (NADH, 460 nm), and flavin adenine dinucleotide (FAD, 550 nm). For DRS, we performed a similar analysis near the peaks of strong absorbers, oxyhemoglobin (oxyHb; 414 nm, 540 nm, and 576 nm) and deoxyhemoglobin (deoxyHb; 432 nm and 556 nm). Logistic regression analysis for these parameters was performed in the testing set. RESULTS: We acquired 17,735 spectra of cancer tissues and 9438 of normal tissues from 30 patients. Intensity peaks of representative normal spectra for FS and DRS were higher than those of representative cancer spectra. Logistic regression analysis showed wavelength and intensity at peaks, and the intensities of the peak wavelength of NADH, FAD, deoxyHb, and oxyHb had significant coefficients. The area under the receiver operating characteristic curve was 0.927. The scanner had 100%, 64.3%, and 85.3% sensitivity, specificity, and accuracy, respectively. CONCLUSIONS: The spectroscopic tissue scanner has high sensitivity and accuracy and provides real-time intraoperative resection margin assessments and should be further investigated as an alternative to frozen section.

Molecular screening of antimalarial, antiviral, anti-inflammatory and HIV protease inhibitors against spike glycoprotein of coronavirus.

Coronavirus outbreak in December 2019 (COVID-19) is an emerging viral disease that poses major menace to Humans and it's a crucial need to find the possible treatment strategies. Spike protein (S2), a envelop glycoprotein aids viral entry into the host cells that corresponds to immunogenic ACE2 receptor binding and represents a potential antiviral drug target. Several drugs such as antimalarial, antibiotic, anti-inflammatory and HIV-protease inhibitors are currently undergoing treatment as clinical studies to test the efficacy and safety of COVID-19. Some promising results have been observed with the patients and also with high mortality rate. Hence, there is a need to screen the best CoV inhibitors using insilico analysis. The Molecular methodologies applied in the present study are, Molecular docking, virtual screening, drug-like and ADMET prediction helps to target CoV inhibitors. The results were screened based on docking score, H-bonds, and amino acid interactions. The results shows HIV-protease inhibitors such as cobicistat (-8.3kcal/mol), Darunavir (-7.4kcal/mol), Lopinavir (-9.1kcal/mol) and Ritonavir (-8.0 kcal/mol), anti-inflammatory drugs such as Baricitinib (-5.8kcal/mol), Ruxolitinib (-6.5kcal/mol), Thalidomide (-6.5kcal/mol), antibiotic drugs such as Erythromycin(-9.0kcal/mol) and Spiramycin (-8.5kcal/mol) molecules have good affinity towards spike protein compared to antimalarial drugs Chloroquine (-6.2kcal/mol), Hydroxychloroquine (-5.2kcal/mol) and Artemisinin (-6.8kcal/mol) have poor affinity to spike protein. The insilico pharmacological evaluation shows that these molecules exhibit good affinity of drug-like and ADMET properties. Hence, we propose that HIVprotease, anti-inflammatory and antibiotic inhibitors are the potential lead drug molecules for spike protein and preclinical studies needed to confirm the promising therapeutic ability against COVID-19.

Targeting Natural Products for the Treatment of COVID-19 - An Updated Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing, rapidly spreading pandemic caused by Severe Acute Respiratory Syndrome Coronavirus2 (SARS-CoV2). Among all the infected countries around the globe as of now (June 15, 2020), the total confirmed positive cases reported are 7,805,148, with the death of 431,192. At present, no specialized treatments evolved to cure COVID-19. Its treatment is symptomatic. Though huge efforts are being made to produce potential therapies to scuffle COVID-19, no drug has been discovered so far. OBJECTIVE: Natural products have been playing a significant role in disease control since ancient days. These products serve as templates for designing new anti-microbial agents with a different mechanism of action and also open a door for investigation of effective anti-viral drugs to combat COVID-19. By focusing on this, the authors have narrated the basic structure, infection, and pathogenesis of SARS-CoV2 virus in humans and also reported various natural products or plant-based extracts/bioactive compounds tested against coronaviruses like SARS and MERS, as these viruses are structurally similar to SARS-CoV2 and can be used in designing novel drug against this virus. CONCLUSION: The natural products having the potential to combat SARS, MERS, and other viruses reviewed in this review article might have anti-viral activities against the SARS-CoV2 virus and can be used directly for further preclinical studies. Therefore, all efforts should be focused on overcoming this serious problem to save many people's lives all over the world.

Spectrochemical Probing of MicroRNA Duplex Using Spontaneous Raman Spectroscopy for Biosensing Applications.

MicroRNAs are emerging as both diagnostic and therapeutic targets in different human pathologies. An accurate understanding of the structural dependency of microRNAs for their biological functions is essential for designing synthetic oligos with various base and linkage modifications that can transform into highly sensitive diagnostic devices and therapeutic molecules. In this proof-of-principle study, we have utilized label-free spontaneous Raman spectroscopy to understand the structural differences in sense and antisense microRNA-21 by hybridizing them with complementary RNA and DNA oligos. Overall, the results suggest that the changes in the Raman band at 785 cm-1 originating from the phosphodiester bond of the nucleic acid backbone, linking 5' phosphate of the nucleic acid with 3' OH of the other nucleotide, can serve as a marker to identify these structural variations. Our results support the application of Raman spectroscopy in discerning intramolecular (ssRNA and ssDNA) and intermolecular (RNA-RNA, RNA-DNA, and DNA-DNA hybrids) interactions of nucleic acids. This is potentially useful for developing biosensors to quantify microRNAs in clinical samples and to design therapeutic microRNAs with robust functionality.

Analysis of subcutaneous swine fat via deep Raman spectroscopy using a fiber-optic probe.

Since the fat content of pork is a deciding factor in meat quality grading, the use of a noninvasive subcutaneous probe for real-time in situ monitoring of the fat components is of importance to vendors and other interested parties. In this work, we developed a spectroscopic method using a fiber-optic probe for subcutaneous fat analysis that utilizes spatially offset Raman spectroscopy (SORS). Here, normalized Raman spectra were acquired as a function of spatial offset, and the relative composition of fat-to-skin was determined. We found that the Raman intensity ratio varied disproportionately depending on the fat content and that the variations of the slope were correlated to the thickness of the fat layer. Furthermore, ordinary least square (OLS) regression using two components indicated that the depth-resolved SORS spectra reflected the relative thickness of the fat layer. We concluded that the local distribution of subcutaneous fat could be measured noninvasively using a pair of fiber-optic probes.

Direct observation of glucose fingerprint using in vivo Raman spectroscopy.

Noninvasive blood glucose monitoring has been a long-standing dream in diabetes management. The use of Raman spectroscopy, with its molecular specificity, has been investigated in this regard over the past decade. Previous studies reported on glucose sensing based on indirect evidence such as statistical correlation to the reference glucose concentration. However, these claims fail to demonstrate glucose Raman peaks, which has raised questions regarding the effectiveness of Raman spectroscopy for glucose sensing. Here, we demonstrate the first direct observation of glucose Raman peaks from in vivo skin. The signal intensities varied proportional to the reference glucose concentrations in three live swine glucose clamping experiments. Tracking spectral intensity based on linearity enabled accurate prospective prediction in within-subject and intersubject models. Our direct demonstration of glucose signal may quiet the long debate about whether glucose Raman spectra can be measured in vivo in transcutaneous glucose sensing.

A Prospective Crossover Study Evaluating the Efficacy of King Vision Video Laryngoscope in Patients Requiring General Anesthesia with Endotracheal Intubation.

BACKGROUND: Direct laryngoscopy used for tracheal intubation requires aligning the pharyngeal, laryngeal and oral axes to achieve a line of sight. Video laryngoscopy provides a better view of the glottis without the need for aligning the three axes. AIMS: To evaluate the effectiveness of King vision laryngoscope over Macintosh laryngoscope in visualizing the glottis and intubating the trachea, when used on a same patient as in a cross over manner. SETTINGS AND DESIGN: Department of Anaesthesia, Mediciti Institute of Medical Sciences, prospective crossover study conducted over a period of six months. SUBJECTS AND METHODS: Sixty adult patients belonging to ASA physical status class I-II, requiring tracheal intubation were randomly assigned to intubation by King vision or Macintosh laryngoscope. Improvement, if any, in the Cormack-Lehane grading using the King vision scope, following initial grading with the Macintosh blade in the same patient was analyzed. STATISTICAL ANALYSIS: Mean and Standard deviation were calculated for different parameters under the study. Where appropriate, results were analyzed using the Mc Nemar χ2 test. A 'p' value less than 0.05 was considered statistically significant. RESULTS: In the King Vision group, Cormack and Lehane grade improved in the majority (9/12) of patients in whom the initial Cormack and Lehane grade was >1 using the Macintosh blade. CONCLUSIONS: The use of the King vision blade significantly improved the laryngoscopic view over the Macintosh blade but the time for intubation was prolonged.

Ultrasound-Guided Subclavian Perivascular Brachial Plexus Block Using 0.5% Bupivacaine with Dexmedetomidine as an Adjuvant: A Prospective Randomized Controlled Trial.

BACKGROUND: Ultrasound guidance has dramatically improved the accuracy of nerve localization, and various adjuvants prolong the block and extend analgesia. AIMS: This study aimed to evaluate the effects of dexmedetomidine added to 0.5% bupivacaine on the onset and duration of motor and sensory blockade and the duration of analgesia. SETTINGS AND DESIGN: This is a prospective, randomized double-blind, study. MATERIALS AND METHODS: Sixty adult patients aged 20-60 years of either sex undergoing orthopedic procedures on the forearm were randomly allocated into two groups of thirty each: Group BS (bupivacaine + saline) and Group BD (bupivacaine + dexmedetomidine). All patients were administered subclavian perivascular brachial plexus block under ultrasound guidance. Group BS: Patients in this group were administered 20-mL 0.5% bupivacaine + 0.75-mL saline. Group BD: Patients in this group were administered 20-mL 0.5% bupivacaine + 0.75-mL dexmedetomidine (75 µg). STATISTICAL ANALYSIS: Statistical analysis was performed with IBM SPSS software Version 21.0. Quantitative data were expressed as mean ± standard deviation. Independent sample t-test was used for comparisons between the two groups. P < 0.05 was considered statistically significant. RESULTS: Demographic data and surgical characteristics were similar in both groups. The onset times for sensory and motor blocks were statistically significantly shorter in Group BD compared to Group BS (P < 0.01), whereas the duration of blocks and analgesia were statistically significantly longer (P < 0.01) in Group BD. CONCLUSION: The addition of dexmedetomidine to 0.5% bupivacaine for supraclavicular brachial plexus block shortens the onset time and prolongs both the duration of the block and analgesia.

In vivo detection of drug-induced apoptosis in tumors using Raman spectroscopy.

We describe a label-free approach based on Raman spectroscopy, to study drug-induced apoptosis in vivo. Spectral-shifts at wavenumbers associated with DNA, proteins, lipids, and collagen have been identified on breast and melanoma tumor tissues. These findings may enable a new analytical method for rapid readout of drug-therapy with miniaturized probes.

Label-free spectrochemical probe for determination of hemoglobin glycation in clinical blood samples.

Glycated hemoglobin, HbA1c, is an important biomarker that reveals the average value of blood glucose over the preceding 3 months. While significant recent attention has been focused on the use of optical and direct molecular spectroscopic methods for determination of HbA1c, a facile test that minimizes sample preparation needs and turnaround time still remains elusive. Here, we report a label-free approach for identifying low, mid and high-HbA1c groups in hemolysate and in whole blood samples featuring resonance Raman (RR) spectroscopy and support vector machine (SVM)-based classification of spectral patterns. The diagnostic power of RR measurements stems from its selective enhancement of hemoglobin-specific features, which simultaneously minimizes the blood matrix spectral interference and permits detection in the native solution. In this pilot study, our spectroscopic observations reveal that glycation of hemoglobin results in subtle but reproducible changes even when detected in the whole blood matrix. Leveraging SVM analysis of the principal component scores determined from the RR spectra, we show high degree of accuracy in classifying clinical specimen. We envisage that the promising findings will pave the way for more extensive clinical specimen investigations with the ultimate goal of translating molecular spectroscopy for routine point-of-care testing.

High-performance serial block-face SEM of nonconductive biological samples enabled by focal gas injection-based charge compensation.

A longstanding limitation of imaging with serial block-face scanning electron microscopy is specimen surface charging. This charging is largely due to the difficulties in making biological specimens and the resins in which they are embedded sufficiently conductive. Local accumulation of charge on the specimen surface can result in poor image quality and distortions. Even minor charging can lead to misalignments between sequential images of the block-face due to image jitter. Typically, variable-pressure SEM is used to reduce specimen charging, but this results in a significant reduction to spatial resolution, signal-to-noise ratio and overall image quality. Here we show the development and application of a simple system that effectively mitigates specimen charging by using focal gas injection of nitrogen over the sample block-face during imaging. A standard gas injection valve is paired with a precisely positioned but retractable application nozzle, which is mechanically coupled to the reciprocating action of the serial block-face ultramicrotome. This system enables the application of nitrogen gas precisely over the block-face during imaging while allowing the specimen chamber to be maintained under high vacuum to maximise achievable SEM image resolution. The action of the ultramicrotome drives the nozzle retraction, automatically moving it away from the specimen area during the cutting cycle of the knife. The device described was added to a Gatan 3View system with minimal modifications, allowing high-resolution block-face imaging of even the most charge prone of epoxy-embedded biological samples.

Differential diagnosis of otitis media with effusion using label-free Raman spectroscopy: A pilot study.

Otitis media with effusion (OME) is an important and common condition affecting hearing in pediatric patients characterized by the presence of fluid in the middle ear space. The fluid is normally described as serous or mucoid based on differences in the fluid viscosity. The differential diagnosis of two OMEs, namely serous and mucoid is of significant clinical value because while the former is self-limiting, surgical procedure is commonly required for the latter. However, accurate identification of fluid types remains a challenging target unattainable with current clinical modalities due to unavailability of nonperturbative molecular tools. Here, we report an emerging spectroscopy approach featuring Raman scattering and multivariate analysis of spectral patterns to discern serous and mucoid fluids, obtained from pediatric patients undergoing myringotomy and tube placement, by providing information of differentially expressed molecules with high specificity. We demonstrate the feasibility of Raman spectroscopy-based approach to categorize middle ear effusion based on the characteristic spectral markers, notably of mucin, with classification accuracy of 91% and 93% for serous and mucoid, respectively. Our findings pave the way for further development of such a tool for fully noninvasive application that will lead to objective and accurate diagnosis thereby reducing unnecessary visits and surgical procedures.

Modeling the depth-sectioning effect in reflection-mode dynamic speckle-field interferometric microscopy.

Unlike most optical coherence microscopy (OCM) systems, dynamic speckle-field interferometric microscopy (DSIM) achieves depth sectioning through the spatial-coherence gating effect. Under high numerical aperture (NA) speckle-field illumination, our previous experiments have demonstrated less than 1 µm depth resolution in reflection-mode DSIM, while doubling the diffraction limited resolution as under structured illumination. However, there has not been a physical model to rigorously describe the speckle imaging process, in particular explaining the sectioning effect under high illumination and imaging NA settings in DSIM. In this paper, we develop such a model based on the diffraction tomography theory and the speckle statistics. Using this model, we calculate the system response function, which is used to further obtain the depth resolution limit in reflection-mode DSIM. Theoretically calculated depth resolution limit is in an excellent agreement with experiment results. We envision that our physical model will not only help in understanding the imaging process in DSIM, but also enable better designing such systems for depth-resolved measurements in biological cells and tissues.

Ticagrelor Removal From Human Blood.

The authors devised an efficient method for ticagrelor removal from blood using sorbent hemadsorption. Ticagrelor removal was measured in 2 sets of in vitro experiments. The first set was a first-pass experiment using bovine serum albumin (BSA) solution pre-incubated with ticagrelor, whereas the second set, performed in a recirculating manner, used human blood mixed with ticagrelor. Removal of ticagrelor from BSA solution reached values >99%. The peak removal rate was 99% and 94% from whole blood and 99.99% and 90% from plasma during 10 h and 3 to 4 h of recirculating experiments, respectively. In conclusion, hemadsorption robustly removes ticagrelor from BSA solution and human blood samples.

Investigating Effects of Proteasome Inhibitor on Multiple Myeloma Cells Using Confocal Raman Microscopy.

Due to its label-free and non-destructive nature, applications of Raman spectroscopic imaging in monitoring therapeutic responses at the cellular level are growing. We have recently developed a high-speed confocal Raman microscopy system to image living biological specimens with high spatial resolution and sensitivity. In the present study, we have applied this system to monitor the effects of Bortezomib, a proteasome inhibitor drug, on multiple myeloma cells. Cluster imaging followed by spectral profiling suggest major differences in the nuclear and cytoplasmic contents of cells due to drug treatment that can be monitored with Raman spectroscopy. Spectra were also acquired from group of cells and feasibility of discrimination among treated and untreated cells using principal component analysis (PCA) was accessed. Findings support the feasibility of Raman technologies as an alternate, novel method for monitoring live cell dynamics with minimal external perturbation.

Raman Spectroscopy Differentiates Each Tissue from the Skin to the Spinal Cord: A Novel Method for Epidural Needle Placement?

BACKGROUND: Neuraxial anesthesia and epidural steroid injection techniques require precise anatomical targeting to ensure successful and safe analgesia. Previous studies suggest that only some of the tissues encountered during these procedures can be identified by spectroscopic methods, and no previous study has investigated the use of Raman, diffuse reflectance, and fluorescence spectroscopies. The authors hypothesized that real-time needle-tip spectroscopy may aid epidural needle placement and tested the ability of spectroscopy to distinguish each of the tissues in the path of neuraxial needles. METHODS: For comparison of detection methods, the spectra of individual, dissected ex vivo paravertebral and neuraxial porcine tissues were collected using Raman spectroscopy (RS), diffuse reflectance spectroscopy, and fluorescence spectroscopy. Real-time spectral guidance was tested using a 2-mm inner-diameter fiber-optic probe-in-needle device. Raman spectra were collected during the needle's passage through intact paravertebral and neuraxial porcine tissue and analyzed afterward. The RS tissue signatures were verified as mapping to individual tissue layers using histochemical staining and widefield microscopy. RESULTS: RS revealed a unique spectrum for all ex vivo paravertebral and neuraxial tissue layers; diffuse reflectance spectroscopy and fluorescence spectroscopy were not distinct for all tissues. Moreover, when accounting for the expected order of tissues, real-time Raman spectra recorded during needle insertion also permitted identification of each paravertebral and neuraxial porcine tissue. CONCLUSIONS: This study demonstrates that RS can distinguish the tissues encountered during epidural needle insertion. This technology may prove useful during needle placement by providing evidence of its anatomical localization.

Digital micromirror device-based laser-illumination Fourier ptychographic microscopy.

We report a novel approach to Fourier ptychographic microscopy (FPM) by using a digital micromirror device (DMD) and a coherent laser source (532 nm) for generating spatially modulated sample illumination. Previously demonstrated FPM systems are all based on partially-coherent illumination, which offers limited throughput due to insufficient brightness. Our FPM employs a high power coherent laser source to enable shot-noise limited high-speed imaging. For the first time, a digital micromirror device (DMD), imaged onto the back focal plane of the illumination objective, is used to generate spatially modulated sample illumination field for ptychography. By coding the on/off states of the micromirrors, the illumination plane wave angle can be varied at speeds more than 4 kHz. A set of intensity images, resulting from different oblique illuminations, are used to numerically reconstruct one high-resolution image without obvious laser speckle. Experiments were conducted using a USAF resolution target and a fiber sample, demonstrating high-resolution imaging capability of our system. We envision that our approach, if combined with a coded-aperture compressive-sensing algorithm, will further improve the imaging speed in DMD-based FPM systems.

Less is more: Avoiding the LIBS dimensionality curse through judicious feature selection for explosive detection.

Despite its intrinsic advantages, translation of laser induced breakdown spectroscopy for material identification has been often impeded by the lack of robustness of developed classification models, often due to the presence of spurious correlations. While a number of classifiers exhibiting high discriminatory power have been reported, efforts in establishing the subset of relevant spectral features that enable a fundamental interpretation of the segmentation capability and avoid the 'curse of dimensionality' have been lacking. Using LIBS data acquired from a set of secondary explosives, we investigate judicious feature selection approaches and architect two different chemometrics classifiers -based on feature selection through prerequisite knowledge of the sample composition and genetic algorithm, respectively. While the full spectral input results in classification rate of ca.92%, selection of only carbon to hydrogen spectral window results in near identical performance. Importantly, the genetic algorithm-derived classifier shows a statistically significant improvement to ca. 94% accuracy for prospective classification, even though the number of features used is an order of magnitude smaller. Our findings demonstrate the impact of rigorous feature selection in LIBS and also hint at the feasibility of using a discrete filter based detector thereby enabling a cheaper and compact system more amenable to field operations.