VESCL: an open source 2D vessel contouring library.

PURPOSE: VESCL (pronounced 'vessel') is a novel vessel contouring library for computer-assisted 2D vessel contouring and segmentation. VESCL facilitates manual vessel segmentation in 2D medical images to generate gold-standard datasets for training, testing, and validating automatic vessel segmentation. METHODS: VESCL is an open-source C++ library designed for easy integration into medical image processing systems. VESCL provides an intuitive interface for drawing variable-width parametric curves along vessels in 2D images. It includes highly optimized localized filtering to automatically fit drawn curves to the nearest vessel centerline and automatically determine the varying vessel width along each curve. To support a variety of segmentation paradigms, VESCL can export multiple segmentation representations including binary segmentations, occupancy maps, and distance fields. RESULTS: VESCL provides sub-pixel resolution for vessel centerlines and vessel widths. It is optimized to segment small vessels with single- or sub-pixel widths that are visible to the human eye but hard to segment automatically via conventional filters. When tested on neurovascular digital subtraction angiography (DSA), VESCL's intuitive hand-drawn input with automatic curve fitting increased the speed of fully manual segmentation by 22× over conventional methods and by 3× over the best publicly available computer-assisted manual segmentation method. Accuracy was shown to be within the range of inter-operator variability of gold standard manually segmented data from a publicly available dataset of neurovascular DSA images as measured using Dice scores. Preliminary tests showed similar improvements for segmenting DSA of coronary arteries and RGB images of retinal arteries. CONCLUSION: VESCL is an open-source C++ library for contouring vessels in 2D images which can be used to reduce the tedious, labor-intensive process of manually generating gold-standard segmentations for training, testing, and comparing automatic segmentation methods.

Assessment of the Efficiency for Anesthesia of Two Agents in Teeth Removal: A Split-Mouth Research.

Aim: This study was intended to assess and relate the clinical anesthetic effectiveness of tramadol hydrochloride and lidocaine. Methodology: A clinical randomized split-mouth study was piloted among 40 patients who were otherwise healthy but needed to have their maxillary first premolars extracted bilaterally for orthodontic reasons were considered in the research. In each subject on one side (quadrant) of the arch 1.8 milliliters of lidocaine was given and on other side of the arch 1.8 milliliters of tramadol was given. On the basis of a list that was prepared by a computer, the randomization was done and the sides (quadrant) of the arches were decided for all the subjects, and the injections were given as local infiltration. Results: Lidocaine was found to be statistically more effective for overall anesthesia duration, despite the fact that there was no significant variance between the two drugs at the time when anesthetic effect began to take effect. Tramadol was found to be statistically more efficient than lidocaine when compared to the anesthetic activity at the 5th minute before extraction. Tramadol was found to be statistically more successful than lidocaine for both the patient's degree of satisfaction and the rate at which wounds healed. Conclusion: Based on the findings of this research, it appears that tramadol and epinephrine could be used as a substitute to conventional local anesthetics during extractions of maxillary first premolar teeth during oral-maxillofacial surgery.

Antibacterial and biofilm disruptive nonribosomal lipopeptides from Streptomyces parvulus against multidrug-resistant bacterial infections.

BACKGROUND: In recent years, new drugs for the treatment of various diseases, thereby the emergence of antimicrobial resistance tremendously increased because of the increased consumption rate of various drugs. However, the irrational use of antibiotics increases the microbial resistance along with that the frequency of mortality associated with infections is higher. Broad-spectrum antibiotics were effectively against various bacteria and the unrestricted application of antibiotics lead to the emergence of drug resistance. The present study was aimed to detect the antibacterial properties of lipopeptide novel drug producing Streptomyces parvulus. METHODS: A lipopeptide-producing S. parvulus was isolated from the soil sample. The inhibitory effect of lipopeptide was detected against Gram-positive and Gram-negative bacteria. Bactericidal activity and minimum inhibitory concentration (MIC) were assayed. The IC50 value was analysed against ovarian and human melanoma cell lines. The experimental mouse model was infected withKlebsiella pneumoniae and treated with lipopeptide and bactericidal activity was determined. RESULTS: The results indicated that the antibacterial activity of lipopeptide ranges from 13 ± 1 mm to 32 ± 2 mm against Gram-positive and Gram-negative strains. The lowest MIC value was noted as 1.5 ± 0.1 µg/mL against K. pneumoniae and the highest against E. aerogenes (7.5 ± 0.2 µg/mL). The IC50 value was considerably high for the ovarian cell lines and human melanoma cell lines (426 µg/mL and 503 µg/mL). At 25 µg/mL concentration of lipopeptide, only 16.4% inhibition was observed in the ovarian cell line whereas 20.2% inhibition was achieved at this concentration in the human melanoma cell line. Lipopeptide inhibited bacterial growth and was completely inhibited at a concentration of 20 µg/mL. Lipopeptide reduced bacterial load in experimental mice compared to control (p < 0.05). CONCLUSION: Lipopeptide activity and its non-toxic nature reveal that it may serve as a lead molecule in the development of a novel drug.

Diagnostic Dilemma of Vanishing Bone Disease - A Case Report and Review of Literature.

Rationale: Vanishing bone disease (VBD) is a rare bone disorder in which progressive osteolysis may lead to complete disappearance of involved bones. The diagnosis of this disease requires a high degree of clinical suspicion. We present a case of progressive osteolysis of mandible in a patient. Patient Concerns: The patient had been without definitive diagnosis and treatment for over a year. Diagnosis: Diagnosis was made by exclusion of genetic, traumatic, inflammatory, infective, endocrine and neoplastic aetiologies and by carefully correlating clinical, imaging and histopathological findings of the patient. Treatment: Segmental resection of the advancing edge of the lesion was carried out. Outcome: The patient is disease free, with no evidence of further osteolysis, after six months of follow-up. Take-Away Lessons: This article describes the exclusion-based approach adopted to diagnose a case of VBD, aiming to standardise a workup for the diagnosis.

Molecular docking of monkeypox (mpox) virus proteinase with FDA approved lead molecules.

BACKGROUND: Monkeypox virus (mpox) disease is caused by a double-stranded DNA virus from the Poxviridae family. The mpox virus showed structural similarity with smallpox virus disease. The recent outbreak of mpox infection in the rest of African countries causes public health issues of increased pandemic potential. Mpox virus is involved in the viral replication cycle through the biocatalytic reaction of precursor polyproteins cleavage. OBJECTIVES: The main objective of the study was to analyze the molecular interactions between mpox and FDA-approved drugs. METHODS: The primary and secondary structure of the protein was retrieved and FDA approved drug was screened using AutoDock. The best hit was analyzed and the molecular interactions were studied. Model validation analyzes the peptide, energy of hydrogen bonds, steric conflicts and bond planarity. Z-score was calculated using ProSA-web tool and the score tested the native fold from other alternative folds. RESULTS: The confidence level of the submitted amino acids was> 80 % and the maximum confidence score for a single template was 98.2 %. The generated proteinase model was subjected to analyze the distribution of atoms and the using ERRAT server. The overall quality score was 88.535 and this value represents the amino acid percentage with anticipated error value and the value falling below the rejection limit. The Z-score of this study result was within the Z-score range (-4.17) validated for native enzymes. The binding pockets of the enzyme were determined in this study and two binding pockets were predicted using the automatic online tool using the web server. The selected FDA-approved drugs were ordered based on their minimum binding energy to the proteinase. CONCLUSIONS: Molecular docking studies revealed the involvement of various hydrophobic interactions between FDA-approved drugs and amino acid residues of monkeypox virus proteinase.

Development of a numerical model for sector-average plume gamma dose and its validation with dose rate measurements at Kalpakkam NPP site, India.

A Gaussian Plume based simple numerical model, named DIFFUSE is developed to simulate the long-term sector-average plume gamma dose due to radioactive plume released during normal operation of nuclear facilities. DIFFUSE calculates site specific joint frequency distributions of wind speed, wind direction and atmospheric stability using micrometeorological observations. It performs the finite sector-average dose integration for any stack height and gamma energy using Simpson's 1/3rd method with sufficient computational efficiency within the site boundary up to 2 km. Plume dose contribution to the main plume sector from nearest and next nearest side plume sectors is also calculated. DIFFUSE is validated with a 3-month long, starting from February 2021 to April 2021, dose rate observation data during operational releases from 100 m stack of Madras Atomic Power Station, Kalpakkam, India. Meteorological data from onsite 50 m tower and continuous dose rate observation from two sets of Autonomous Gamma Dose Logger (AGDL) detectors, namely n-AGDLs and r-AGDLs, placed in two different configurations along the geometric arcs of wind sectors around the stack are used. Simulated doses are compared with look-up table based dose estimates by Hukkoo et al. (1988). Linear spatial averaging of cumulative AGDL doses on a sector arc is used as measured sector-average dose for model validation. Simulations performed for both n-AGDL and r-AGDL configurations show DIFFUSE estimated doses are ∼37% lower and Hukkoo estimated doses are at least ∼50% lower than the measured doses. Statistical analysis of DIFFUSE simulated doses shows a statistical correlation of R2∼98.3%, slope of the fit ∼1.36 for n-AGDL setup and R2∼75.3%, slope of the fit ∼1.57 for r-AGDL setup. Overall, DIFFUSE produces conservative doses compared to look-up table based doses as required by regulatory bodies.

Lightning Characteristics Over Humid Regions and Arid Regions and Their Association With Aerosols Over Northern India.

The association between aerosol and lightning has been investigated with long-term decadal data (2005-2014) for lightning, aerosol optical depth (AOD), relative humidity, and effective cloud droplet size. To understand the complex relationship between aerosol and lightning, two different regions with different climatic and weather conditions, a humid region R1 (22°-29° N, 89°-92° E) and an arid region R2 (23°-28° N, 70°-76° E) of northern India, were chosen for the study domain. The results show that lightning activity was observed to occur more over the humid region R1, i.e., 1141 days (1/3 of total days), than over the arid region R2, i.e., 740 days (1/5 of total days). Also, over the humid region R1, the highest lightning flash density was recorded as nearly 4.6 × 10-4 flashes/km2/day observed for 18 days (1.5%); on the contrary, over the arid region R2, the maximum lightning flash density was observed to be 2.5 × 10-4 flashes/km2/day and occurred for about 22 days (2.9%). The analysis shows that a nonlinear relationship exists between aerosol and lightning with a highly associated influence of relative humidity. A very significant positive and negative co-relation that varies with relative humidity has been observed between AOD and lightning for both humid and arid regions. This shows relative humidity is the key factor in determining the increase or decrease of lightning activity. This study also shows that the larger the cloud droplet size, the higher the relative humidity and vice versa. This study emphasizes that aerosol concentration in the atmosphere influences cloud microphysics by modulating the size of cloud droplets and thereby regulating the lightning frequency. The atmospheric humidity is the driving factor in deciding the positive or negative co-relationship between aerosol and lightning. Supplementary Information: The online version contains supplementary material available at 10.1007/s00024-022-02981-6.

Intervention strategies for microbial therapeutics in cancer immunotherapy.

Immunotherapies have drastically improved clinical outcomes in a wide range of malignancies. Nevertheless, patient responses remain highly variable, and reliable biomarkers that predict responses accurately are not yet fully understood. Compelling evidence from preclinical studies and observational data from clinical cohorts have shown that commensal microorganisms that reside in the human gastrointestinal tract, collectively termed the 'microbiome', can actively modify responses to chemotherapeutic agents and immunotherapies by influencing host immunosurveillance. Notably, microbial correlates are largely context specific, and response signatures may vary by patient population, geographic location and type of anticancer treatment. Therefore, the incongruence of beneficial microbiome signatures across studies, along with an emerging understanding of the mechanisms underlying the interactions between the microbiome, metabolome and host immune system, highlight a critical need for additional comprehensive and standardized multi-omics studies. Future research should consider key host factors, such as diet and use of medication, in both preclinical animal models and large-scale, multicenter clinical trials. In addition, there is a strong rationale to evaluate the microbiome as a tumor-extrinsic biomarker of clinical outcomes and to test the therapeutic potential of derived microbial products (e.g. defined microbial consortia), with the eventual goal of improving the efficacy of existing anticancer treatments. This review discusses the importance of the microbiome from the perspective of cancer immunotherapies, and outlines future steps that may contribute to wide-ranging clinical and translational benefits that may improve the health and quality of life of patients with cancer.

Purification and characterization of ß-galactosidase from newly isolated Aspergillus terreus (KUBCF1306) and evaluating its efficacy on breast cancer cell line (MCF-7).

ß-galactosidases (EC 3.2.1.23) are able to catalyze two different types of reactions, namely hydrolysis and transgalactosylation. It is a lysosomal exoglycosidase involved in the catabolism of glycoconjugates by sequential release of ß-linked terminal galactosyl residues. It has profound significance in cancer cell senescence. It can be derived from microbial sources including bacteria, yeasts, and filamentous fungi. The enzyme was purified from the crude enzyme using ammonium sulfate precipitation, dialysis, ion exchange chromatography using DEAE cellulose, fast protein liquid chromatography and high performance liquid chromatography. The enzyme was purified with 10.78 -fold with specific activity of 62 U/mg of protein and yield of 28.26%. Molecular weight of ß -galactosidase as estimated by using SDS-PAGE was 42 kDa. Kinetic parameters Km and Vmax for purified enzyme were 0.48 and 0.96 respectively. Further the characterization and kinetic studies of purified enzyme were carried out. The optimum pH and temperature for maximum ß-galactosidase activity were found to be 6, 40 °C, respectively. The present study is aimed to purification, characterization and in vitro efficacy assessment in breast cancer cell line. The ß-galactosidase isolated from Aspergillus terreus was found to be effective in the proliferation of MCF-7 breast cancer cells in vitro. The present study is aimed to purification and characterization of enzyme to assess in vitro efficacy of ß-galactosidase on MCF-7 cell line to delineate its therapeutic efficacy.

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Mandibular fracture in a neonate.

Mandibular fractures in the neonate are rare. The aetiological factors are traumatic delivery, accidental fall, road traffic accidents, and attempted infanticide. The diagnosis is difficult due to facial oedema masking the clinical features and the absence of dentition. The treatment of fractures in the newborn represents a unique problem in terms of investigations, diagnosis, selection of anaesthesia, and method of fixation. The case of a 1-day-old infant referred for the management of a mandibular fracture sustained in an accidental fall is presented herein. During oral suctioning, the neonatologist observed continuous blood-stained secretions, which raised the suspicion of a trauma to the oral cavity. The infant was diagnosed as having a fracture of the mandibular symphysis with displacement. The fracture was reduced under local anaesthesia with sedation, and was stabilized with an acrylic splint, which was secured with circum-mandibular wiring. The patient was followed up for 1.5 years and the healing was satisfactory.

Design and implementation of wireless dose logger network for radiological emergency decision support system.

A decision support system (DSS) is implemented in Radiological Safety Division, Indira Gandhi Centre for Atomic Research for providing guidance for emergency decision making in case of an inadvertent nuclear accident. Real time gamma dose rate measurement around the stack is used for estimating the radioactive release rate (source term) by using inverse calculation. Wireless gamma dose logging network is designed, implemented, and installed around the Madras Atomic Power Station reactor stack to continuously acquire the environmental gamma dose rate and the details are presented in the paper. The network uses XBee-Pro wireless modules and PSoC controller for wireless interfacing, and the data are logged at the base station. A LabView based program is developed to receive the data, display it on the Google Map, plot the data over the time scale, and register the data in a file to share with DSS software. The DSS at the base station evaluates the real time source term to assess radiation impact.

Stress perceived by houseman in a hospital in northern Malaysia.

INTRODUCTION: Being a houseman in Malaysian hospitals can be very stressful. Stress can affect decision making to a great extent while addressing the needs of the patient in an emergency setting. This necessitated a study to find out the main sources of stress among housemen. METHODS: This was a cross-sectional descriptive study carried out among 55 housemen using a questionnaire on sources of stress. The data was analysed using SPSS version 17. RESULTS: A total of 16 factors leading to stress were studied among the housemen. Poor work and social life balance, annoying non-clinical personnel and medico-legal threats were among the top causes of stress. CONCLUSION: The factors leading to stress among housemen should be considered for effective working of the hospital and improving the workplace atmosphere for the housemen.

Remineralizing potential of CPP-ACP applied for 1 min in vitro.

AIM: To evaluate (1) the remineralizing potential of Tooth Mousse(®) (TM) on artificial carious lesions, when applied for 1 min, and (2) the benefit of a fluoridated dentifrice prior to TM application. METHODS: Demineralisation caries-like lesions 120-200 µm deep were produced by placing molars in demineralizing solution for 96 h, sections 100-150 µm thick were then randomly assigned to four groups. Specimens were treated thrice daily with a non-fluoridated (Group A), or fluoridated dentifrice (1000 ppm) (Group B), or TM (Group C), or a fluoridated dentifrice followed by TM (Group D) then subjected to a 10-day pH cycling model. Lesion evaluation involved polarizing light microscopy and microradiography. RESULTS: Application of TM in isolation (Group C) for 1 min resulted in significant increase in lesion depth (LD), however, an increase in mineral content deposition (V max) was not significant. Post treatment LD increases were greatest in Group A, then Group C and Group B respectively. A decrease in LD (by 19.9 %) was noted only after fluoridated dentifrice and TM (Group D) were applied consecutively for 1 min each (p < 0.05). Mineral content deposition was also greatest in this group (Group D) and both V max and LD changes were statistically significant when compared to other groups. CONCLUSIONS: TM alone failed to remineralize carious lesions when applied for 1 min. However, remineralization occurred after a prior application of a fluoridated dentifrice.

Note: Design and development of wireless controlled aerosol sampling network for large scale aerosol dispersion experiments.

Wireless based custom built aerosol sampling network is designed, developed, and implemented for environmental aerosol sampling. These aerosol sampling systems are used in field measurement campaign, in which sodium aerosol dispersion experiments have been conducted as a part of environmental impact studies related to sodium cooled fast reactor. The sampling network contains 40 aerosol sampling units and each contains custom built sampling head and the wireless control networking designed with Programmable System on Chip (PSoC™) and Xbee Pro RF modules. The base station control is designed using graphical programming language LabView. The sampling network is programmed to operate in a preset time and the running status of the samplers in the network is visualized from the base station. The system is developed in such a way that it can be used for any other environment sampling system deployed in wide area and uneven terrain where manual operation is difficult due to the requirement of simultaneous operation and status logging.