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Transgalactosylation reaction is the penultimate step in the production of galactooligosaccharides (GOSs) which has prominent applications in the treatment of disorders. In the present study, partially purified β-galactosidase from Enterobacter aerogenes KCTC2190 was used for the synthesis of prebiotic GOSs. GOSs were produced using lactose as substrate. Structural elucidation of collected fractions of GOSs by liquid chromatography electrospray ionization mass spectrometry exhibited the appearance of major peaks of produced GOSs at m/z 241.20, 481.39, 365.11, 527.17, and 701.51 respectively. GOSs facilitated the growth of potential probiotic strains (Lactobacillus delbrueckii ssp. helveticus, Bifidobacterium bifidum, and Lactiplantibacillus plantarum) and liberated propionate and butyrate as principal short-chain fatty acids which established its prebiotic potency. Synbiotic combinations exhibited good antioxidant activities. Synbiotic combinations also exhibited antimicrobial activities against pathogenic microorganisms namely Staphylococcus aureus and Escherichia coli. Synbiotic combinations of GOSs and the respective probiotic microorganisms were able to decrease viable human bone cancer cells (MG-63).

The response of cytoskeleton to mechanical cues plays a pivotal role in understanding several aspects of cellular growth, migration, and cell–cell and cell–matrix interactions under normal and diseased conditions. Finite element analysis (FEA) has become a powerful computational technique to study the response of cytoskeleton in the maintenance of overall cellular mechanics. With the revelation of role of external mechanical microenvironment on cell mechanics, FEA models have also been developed to simulate the effect of substrate stiffness on the mechanical properties of cancer cells. However, the models developed so far model cellular response under static mode, whereas in physiological condition, cells always experience dynamic loading conditions. To develop a more accurate model of cell-extracellular matrix (ECM) interactions, this paper models the cytoskeleton and other parts of the cell by beam and solid elements respectively, assuming spherical morphology of the cell. The stiffness and roughness of extracellular matrix were varied. Furthermore, static and dynamic sinusoidal loads were applied through a flat plate indenter on the cell along with providing sinusoidal strain at the substrate. It is observed that due to axial loading, cell reaches a plastic region, and when the sinusoidal loading is added to the axial load, the cell experiences permanent deformation. Degradation of the cytoskeleton elements and a physiologically more relevant spherical cap shape of the cell were also considered during the analysis. This study suggests that asperity topology of the substrate and indirect cyclic load can play a significant role in the shape alterations and motion of a cell.

Despite different nanomaterials were developed so far against cancer, their potential drawbacks are still scarcely considered. The off-target delivery of a therapeutic compound, as well as the non-specific uptake of these nanomaterials by healthy tissues or organs, and their potential immunogenicity are some of the major issues that still have to be faced prior to a successful clinical translation. This work aims to develop an innovative theranostic, biocompatible, and drug-loaded nanoconstruct based on Gadolinium-doped Zinc Oxide (ZnO-Gd) nanocrystals (NCs), focusing on one of the most lethal diseases, i.e., pancreatic cancer. The use of zinc oxide is motivated by the huge potential of this nanomaterial already demonstrated for in vitro and in vivo applications, while the Gadolinium doping confers magnetic properties useful for diagnostics. Furthermore, an innovative biomimetic shell is here used to coat the NCs: it is composed of a lipid bilayer made from extracellular vesicles (EVs) combined with other synthetic lipids and a peptide targeting the pancreatic tumor microenvironment. To complete the nanoconstruct therapeutic function, Gemcitabine, a first-line drug for pancreatic cancer treatment, was adsorbed on the ZnO-Gd NCs prior to the coating with the above-mentioned lipidic shell. The aim of this work is thus to strongly enhance the therapeutic capability of the final nanoconstruct, providing it with high biocompatibility, colloidal stability in biological media, efficient cargo loading and release properties, as well as active targeting for site-selective drug delivery. Furthermore, the magnetic properties of the ZnO-Gd NCs core can in future allow efficient in situ bioimaging capabilities based on Magnetic Resonance Imaging technique. The obtained nanoconstructs were tested on two different pancreatic cancer cell lines, i.e., BxPC-3 and the metastatic AsPC-1, proving high cell internalization levels, mediated by the targeting peptide exposed on the nanoconstruct. Cellular cytotoxicity assay performed on both cell lines dictated ~ 20% increased cell killing efficacy of Gemcitabine when delivered through the nanoconstruct rather than as a free drug. Taken together, our designed theranostic nanoconstruct can have a significant impact on the standard treatment of pancreatic cancer.

In clinical studies, survival analysis is a well known technique to analyze time to event data with the assumption that every subject in the study will encounter the event of interest. With recent advancements in the drug development industry, a fraction of subjects may not face the event and are considered as immune or cured. However, due to the finite study period, full knowledge of subjects who are immune is usually not known and hence, can be considered as missing. We develop a novel semi-parametric algorithm to address this problem by minimizing a suitable loss function, which incorporates the missing data and generates cure indicators for the censored individuals. We prove the existence of a global minimizer for the loss function and establish some asymptotic properties, demonstrate via numerical experiments that under appropriate circumstances, our approach performs better than simpler alternatives, and use this algorithm to estimate lifetime parameters and the overall survivor function.

Deep neural networks (DNNs) have shown success in image classification, with high accuracy in recognition of everyday objects. Performance of DNNs has traditionally been measured assuming human accuracy is perfect. In specific problem domains, however, human accuracy is less than perfect and a comparison between humans and machine learning (ML) models can be performed. In recognising everyday objects, humans have the advantage of a lifetime of experience, whereas DNN models are trained only with a limited image dataset. We have tried to compare performance of human learners and two DNN models on an image dataset which is novel to both, i.e. histological images. We thus aim to eliminate the advantage of prior experience that humans have over DNN models in image classification. Ten classes of tissues were randomly selected from the undergraduate first year histology curriculum of a Medical School in North India. Two machine learning (ML) models were developed based on the VGG16 (VML) and Inception V2 (IML) DNNs, using transfer learning, to produce a 10-class classifier. One thousand (1000) images belonging to the ten classes (i.e. 100 images from each class) were split into training (700) and validation (300) sets. After training, the VML and IML model achieved 85.67 and 89% accuracy on the validation set, respectively. The training set was also circulated to medical students (MS) of the college for a week. An online quiz, consisting of a random selection of 100 images from the validation set, was conducted on students (after obtaining informed consent) who volunteered for the study. 66 students participated in the quiz, providing 6557 responses. In addition, we prepared a set of 10 images which belonged to different classes of tissue, not present in training set (i.e. out of training scope or OTS images). A second quiz was conducted on medical students with OTS images, and the ML models were also run on these OTS images. The overall accuracy of MS in the first quiz was 55.14%. The two ML models were also run on the first quiz questionnaire, producing accuracy between 91 and 93%. The ML models scored more than 80% of medical students. Analysis of confusion matrices of both ML models and all medical students showed dissimilar error profiles. However, when comparing the subset of students who achieved similar accuracy as the ML models, the error profile was also similar. Recognition of ‘stomach’ proved difficult for both humans and ML models. In 04 images in the first quiz set, both VML model and medical students produced highly equivocal responses. Within these images, a pattern of bias was uncovered–the tendency of medical students to misclassify ‘liver’ tissue. The ‘stomach’ class proved most difficult for both MS and VML, producing 34.84% of all errors of MS, and 41.17% of all errors of VML model; however, the IML model committed most errors in recognising the ‘skin’ class (27.5% of all errors). Analysis of the convolution layers of the DNN outlined features in the original image which might have led to misclassification by the VML model. In OTS images, however, the medical students produced better overall score than both ML models, i.e. they successfully recognised patterns of similarity between tissues and could generalise their training to a novel dataset. Our findings suggest that within the scope of training, ML models perform better than 80% medical students with a distinct error profile. However, students who have reached accuracy close to the ML models, tend to replicate the error profile as that of the ML models. This suggests a degree of similarity between how machines and humans extract features from an image. If asked to recognise images outside the scope of training, humans perform better at recognising patterns and likeness between tissues. This suggests that ‘training’ is not the same as ‘learning’, and humans can extend their pattern-based learning to different domains outside of the training set.

Tissue engineering has been a subject of extensive scientific exploration in the last two decades making gradual inroads into clinical studies as well. Along with regenerative cells and growth factors, biomaterial scaffolds are integral to the development of a tissue engineered construct. It is now appreciated that scaffolds should mimic the target tissue properties intimately in order to provide a micro-environment milieu that allows the seeded cells to differentiate into the desired tissue. Even from a structural viewpoint, mismatch between scaffold and native matrix properties can cause cell necrosis through mechanisms such as stress shielding. One of the key properties of most body tissues is that they exhibit anisotropy. However, most fabrication methods generate isotropic scaffolds and require specific modifications to produce anisotropic scaffolds. In the last decade, the advent of additive manufacturing and bioprinting has provided facile tools to fabricate scaffolds with desired anisotropy. On the other hand, a biomimetic scaffold can be designed only when target tissue anisotropy is well known to the tissue engineer. This review presents an overview of the anisotropic properties of different tissues, which will be critical for developing biomimetic engineered constructs. The traditional anatomical records do not adequately present these properties from the perspective of designing tissue engineering scaffolds. Subsequently, present state-of-the art in development of anisotropic scaffolds as well as tissue constructs using different conventional and emerging fabrication techniques is discussed. It is expected that the readers will obtain a comprehensive reference on the research area by examining these two aspects juxtaposed to each other and gain key trends for fabrication of anisotropic scaffolds, plausibly with improved regenerative outcomes.

Combination of bioceramics with polymers to fabricate nanofibrous scaffolds holds enormous potential for bone tissue regeneration. In this study, we aim to incorporate HAp nanoparticles in trace doping amount in PVA-chitosan nanofiber matrix to fabricate PVA-chitosan composite nanofibers with improved performance for application as a bone tissue regeneration material. The diameter of the fabricated composite nanofibrous mat is estimated as 300 ± 121 nm. Beads free nanofibers mat with uniform morphology was ascertained for all sample groups by scanning electron microscopy (SEM) and the overall composition was assessed using Fourier transform infrared spectroscopy (FTIR) and energy dispersive X-ray spectroscopy (EDX). SEM images showed a homogeneous distribution of HAp nanoparticles in the composite nanofibers matrix. Further, X-ray diffraction (XRD) was performed to determine the crystallinity of the fabricated scaffolds. Swelling behavior and hydrolytic degradation of nanofibrous mats were subsequently evaluated by immersing in PBS buffer at pH 7.4 at physiological temperature (37 °C). The biocompatibility study of nanofiber scaffolds was performed with MC3T3 cells. Significantly higher cellular viability was observed on HAp nanoparticles incorporated composite nanofibrous scaffold surface after 7 days of culture in comparison to scaffolds without HAp.

Background Surgical site infections (SSIs) are among the most common healthcare-associated infections. Under-nutrition is an important risk factor for SSIs and can lead to delayed wound healing and longer hospital stays. Oral nutritional supplements are prescribed to reduce the risk of infection and improve health status, but data from randomised controlled trials (RCTs) have shown mixed results. Thus, the objective of our planned systematic review is to evaluate oral nutritional supplements on preventing SSIs in adult surgical patients Methods RCTs conducted in adult surgical patients who receive oral nutritional support will be included. The primary outcome will be the incidence of SSIs (within 30 days of surgery or within 90 days for joint replacement surgery). Secondary outcomes will be changes in nutritional status, mortality, health-related quality of life and costs. Literature searches will be conducted in several electronic databases (from inception onwards): MEDLINE, Embase, CINAHL and The Cochrane Central Register of Controlled Trials (CENTRAL). Grey literature will be identified through searching clinical trial registers and dissertation databases. Two reviewers will independently screen all citations, full-text articles and abstract data. The study methodological quality (or bias) will be appraised using the Cochrane risk of bias tool. If feasible, we will conduct random effects meta-analysis where appropriate. Discussion This systematic review will evaluate the evidence for pre- and post-surgical intervention with oral nutritional supplements in adults. Findings from this planned review may inform subsequent nutritional interventions for hospitalised patients who undergo surgery. Systematic review registration PROSPERO CRD42020140954

A colorimetric and fluorescence turn-off probe 10-(4-azido phenyl)-5,5-difluoro-5h-dipyrrolo[1,2-c:1’,2’-f][1,3,2] diazaborinin-4-ium-5-uide, 1, for selective detection of H2S is reported. The probe displayed a robust decrease in fluorescence intensity with high sensitivity, specificity and least toxicity to detect exogenous H2S and also in live normal human oral fibroblast cells loaded with probe 1. The detection limit of probe 1 being 0.17 µm for H2S. A colorimetric and fluorescence turn-off BODIPY probe 1, for selective detection of exogenous H2S in live normal human oral fibroblast cells loaded with probe 1 and poisonous H2S gas formed under biodegradation in sewage waters and water tanks and corroded pipe lines. The detection limit of probe 1 being 0.17 μM

Automated identification of healing progression in lower limb wounds is an important clinical challenge since such wounds fail to heal in an orderly and timely manner. Selection of suitable target features and employment of appropriate analytical tool are critical for the precise monitoring of the healing progression through automated diagnostic method. The present study aims at automated detection of healing trend based on characteristics of epithelial rete pegs, which is considered as an important parameter for monitoring and hence healing progression of epithelial maturation. To this aim, the applicability of various segmentation methods namely, watershed, marker-controlled watershed, k-means clustering and active contour method and comprehensive characterization of rete-pegs are studied and compared. Among them active contour provided better performance in terms of non-linear objective assessments including performance metrics like-peak-signal-to-noise-ratio, processing speed and Mean Square Error. Further, support vector machine is trained for classification of the rete-peg features at different time points of clinically diagnosed non-healing wounds treated with a specific protocol. Kappa scoring tests inter-rater agreement between applied segmentation protocol and ground truth images. The overall accuracy of the system has been found to be 95%. It is thus concluded that with the aid of the proposed segmentation and classification method an automated detection system can be developed for precise monitoring of lower limb wound healing progression.

The polysaccharide alginate has received most extensive attention as bioink in bioprinting applications due to its ability to undergo gelation under cell-friendly conditions. However, absence of cell-binding motifs and the erratic degradation of alginate hydrogels have remained their persistent limitations. Honey is a conveniently available natural material, known for its role in wound healing and skin tissue regeneration. However, honey blending to improve biological response of alginate-based bioprinted scaffolds has not been yet reported. In the present work, honey-alginate bioinks were evaluated for their printability property (shape fidelity). It was found that honey blending reduced alginate viscosity, which gradually affected bioprinting fidelity. Therefore, the concentration that provides for acceptable bioprinting along with improvement in cell proliferations is determined. It is concluded that honey blending improves cell response of alginate bioinks and can be a facile approach to obtain bioinks especially for in situ skin tissue engineering applications.

Nanosized reduced graphene oxide (rGO) is found in active microcarbon used in popular face cream from the manufacturers like Ponds, Nevia, and Garnier which, under visible light exposure, gets activated by aerial oxygen to generate reactive oxygen species (ROS) harmful to skin.

Topical application of honey for tissue regeneration, has recently regained attention in clinical practice with controlled studies affirming its efficacy and indicating its role in regeneration over repair. Parallely, to overcome difficulties of applying raw honey, several product development studies like nanofibrous matrices have been reported. However, one approach concentrated on achieving highest possible honey loading in the nanofiber membranes while other studies have found that only specific honey dilutions result in differential cellular responses on wound healing and re-epithelization. From these results, it can be suggested that high honey loading provides optimum external microenvironment, low-loaded membranes could provide a more conducive internal microenvironment for tissue regeneration. With this hypothesis, this paper sought to evaluate ability of low-honey loaded nanofibers to modulate the anti-oxidant, anti-biofilm and anti-inflammatory properties which are important to be maintained in wound micro-environment. A loading-dependent reduction of biofilm formation and anti-oxidant activity was noted in different concentration ranges investigated. After scratch assay, a certain honey loading (0.5%) afforded the maximum re-epithelization. Since there is lack of methods to determine anti-inflammatory properties of nanofiber membranes during epithelial healing process, we performed anti-inflammatory assessment of nano-fibers by evaluating the expressions of pro-inflammatory markers-Cycloxygenase-2 (COX-2) and Interleukin-6 (IL-6) and to confirm the optimized concentration. Considering the role of COX-2 and IL-6, the novel methodology used in this study can also be developed as an assay for anti-inflammatory matrices for wound healing.

The aim of this study was to microencapsulate the reuterin produced by Lactobacillus reuteri BPL-36 strain for its long-term efficacy against food-borne pathogen Listeria monocytogenes. Lactobacillus reuteri BPL-36 strain previously isolated from a human infant fecal sample in lab was selected for the present study based on its ability to produce reuterin. The organism displayed a broad-spectrum antimicrobial activity. Reuterin concentration of 89.63 mM was obtained in the MRS–glycerol medium after 16 h incubation at 37 °C. The reuterin concentration required to inhibit the growth of Pseudomonas aeruginosa, Escherichia coli O157: H7, Salmonella typhi, Staphylococcus aureus, and Listeria monocytogenes was found to be 1.0, 2.0, 2.0, 4.0, and 10.0 AU/mL, respectively. Microencapsulation of reuterin to enhance long-term efficacy against food-borne pathogens was done. Results in this study indicated that the release characteristics of reuterin from the encapsulated particles were pH dependent. The release characteristics were unaffected by the storage of encapsulated reuterin at 4 °C for 2 weeks. The anti-listerial efficacy of the encapsulated reuterin was tested against L. monocytogenes in the BHI medium adjusted to pH 5.0 with a reuterin content equivalent to 16 mM, similar to un-encapsulated (free) reuterin. Encapsulated reuterin demonstrated enhanced efficacy against L. monocytogenes for longer duration of time when compared with un-encapsulated (free) reuterin. The present work demonstrated a novel antimicrobial delivery system that ensured much better capability of inhibiting the growth of L. monocytogenes throughout 24 h incubation at 37 °C.

The degree of increase in foetal haemoglobin (HbF) synthesis in haematological malignancies may be associated with the degree of malignancy. The aim of the present study was to quantify HbF levels in various childhood haematological malignancies and also, to ascertain its prognostic significance by comparing the results with the already established standard prognostic factors. Newly diagnosed cases of haematological malignancies in the paediatric age group were included in the study. HbF levels were estimated in each case of the study group along with HbF levels of control group comprising healthy children of same age group. The estimation was done by HPLC and Modified Betke's method. 50 cases of newly diagnosed haematological malignancies were studied out of which most of the cases were of acute lymphoblastic leukaemia (ALL) [n = 30(60 %)] followed by acute myeloid leukaemia (AML) [n = 8(16 %)], Hodgkin's lymphoma [n = 7(14%)], non-Hodgkin's lymphoma [n = 5(10 %)]. Raised HbF levels were found in 43.3 % cases of ALL (13/30) and 37.5 % cases of AML (3/8). No significant rise in HbF level was found in cases of lymphomas. There was correlation between raised HbF level and poor prognostic factors in cases of ALL but no such correlation was found in cases of AML. HbF levels are often elevated in childhood leukaemias as compared to childhood lymphomas. Thus, the concentration of HbF in acute childhood leukaemia may be considered as a prognostic factor.

The effect of solar eclipse of July 22, 2009, obscuring up to 91 %, upon the value of point discharge current (PDC) has been reported in this paper. The observation had been taken from Kolkata (Lat. 22.56°N, Long. 88.5°E). During the eclipse period, significant variations in the magnitude of PDC were observed than their average value for the same period in other days. The average value of the PDC for the successive ±10 days adjacent to the solar eclipse day was about 2.253 A.U. (Arbitrary Unit), while the minimum value showed about 2.242 A.U. at the time of greatest phase at 06:26.4 IST (Indian Standard Time). The results are mainly interpreted in terms of changes of the conductivity of the medium during the solar eclipse.

A paper chromatographic method for the detection of adulteration of anionic detergent in milk is described. The method is based on the complexing of anionic detergent with methylene blue dye and separation of complex from free dye using simple paper chromatographic method. Since complexing of detergent is with dye, visualization is direct without involvement of subsequent detection of complex. The method is simple and results are available in 10 min. The method is sensitive to detect 0.1 % (w/v) labolene (laboratory grade detergent) or 0.01 % (w/v) sodium dodecylbenzene sulfonate (pure anionic detergent) in milk. The method can be adopted at quality control laboratories in dairies for ascertaining the quality of milk.

The effects of 2009 Leonid Meteor Shower upon the two VLF subionospheric transmitted signals and vertical electric potential gradient from the ground surface have been studied from Kolkata (Lat: 22.56°N, Long: 88.5°E) on November 17, 2009. The received signals showed their peak values when ZHR (Zenithal Hourly Rate) was highest. Some typical variations in the outcome of these measurements during the meteor showers will be presented in this paper.

Absorption and effectiveness of vaginally administered misoprostol tablets may vary according to the medium in which it is placed. This study was directed to compare the outcomes of vaginal administrations of acetic acid-moistened misoprostol tablets with those of dry tablets for induction of second-trimester abortion. A randomized comparative trial where 322 women at 13–20 weeks gestation, requiring medical abortion, were randomly assigned to vaginal administration of either acetic acid-moistened or dry misoprostol tablets with a dose schedule of 400 μg three-hourly, up to a maximum five doses over 24 h. The same doses were repeated for another 24 h in nonresponders. Primary outcome measure was complete abortion rate at 24 and 48 h, and the secondary outcome measures were induction–abortion interval, failure rate and side effects. A difference of 15% in success rates at 24 h was used to calculate the sample size required with a power of 0.8 at the 5% significance level. No statistically significant differences in the complete abortion rates were observed at 24 h (70.95 vs. 68.71%, P = 0.675) and at 48 h (86.49 vs. 84.35%, P = 0.604) when both groups were compared. The difference in mean induction–abortion interval was also statistically insignificant between the groups (12.5 ± 1.6 vs. 12.8 ± 1.5 h, P = 0.97). Other outcome measures were also comparable in both groups. Moistening misoprostol tablets with 5% acetic acid before vaginal application creates no difference in outcomes when compared with those after the vaginal application of dry tablets for the termination of second-trimester pregnancy.

The detection of 2009 Leonid, Perseid and Geminid meteor showers over Agartala, Tripura, India (Lat: 23.0° N, Long: 91.4° E) will be reported here by using two VLF receivers tuned to subionospheric transmitted VLF signals at the frequency 16.4 kHz from Aldra Island, Norway (Lat: 66.42° N, Long: 13.13° E) and the other at 18.2 kHz from Vijayananarayanam, India (Lat: 8.4° N; Long: 77.7° E). The received signals exhibited their peak values on November 17, 2009 when ZHR (Zenithal Hourly Rate) was highest. Some typical variations which are observed in the records of amplitude during the 2009 Leonid, Perseid and Geminid meteor showers will be presented in this paper.

Several experiments were undertaken at Kolkata (latitude: 22°34′N, longitude: 88°30′E) on the solar eclipse day of August 1, 2008 to observe the effects of the solar eclipse on Fair Weather Field (FWF) and VLF amplitude and phase. The experimental results presented here show significant deviations of the observed parameters from their normal values, as they are determined by the average of the records obtained on 5 days adjacent to the day of the solar eclipse.

Continuous recording of a subionospheric transmitted signal at 16.4 kHz from Novik, Norway (66° 58′ N, 13° 54′ E) is being carried out in Kolkata (22° 34′ N, 88° 30′ E). The effects of recent solar eclipse on August 1, 2008 over this transmitted signal have been reported in this paper. The variations of normalized amplitude of this signal and its phase retardation in the path during the solar eclipse are measured which show significant deviations from their usual values for the same period of the control days.