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.

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.

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.

Terpenoids Isolated From the Shoot of Plectranthus hadiensis Induces Apoptosis in Human Colon Cancer Cells Via the Mitochondria-Dependent Pathway.

The plant Plectranthus hadiensis is a rich source of many bioactive phytochemicals, especially terpenoids. The terpenoid fraction was isolated and phytochemical characterization was done using GC-MS. The aim of the present study was to find out the antiproliferative activity and the mechanism of cell death induction by the terpenoid fraction on human colon cancer cells (HCT-15). MTT assay was performed with different concentrations of the fraction (10, 20, and 50 µg/mL) to obtain IC50 value for 24 h to induce cell death. The induction of apoptosis were studied by Hoechst staining, acridine orange/ethidium bromide staining, Comet assay, DNA fragmentation, and caspase-3 activity assays. The mechanism of apoptosis induction was studied by expression analysis of antiapoptotic Bcl-2 and proapoptotic Bax using RT-PCR and also by Western blot analysis of proteins involved in the apoptotic pathway. The terpenoid fraction induced significant morphological changes and DNA fragmentation in the cells. Positive Hoechst staining and acridine orange/ethidium bromide staining indicated apoptosis induction by the fraction. DNA fragmentation, which is a characteristic feature of apoptosis, was also observed. Upregulation of caspase-3 activity and proapoptotic Bax, and the downregulation of antiapoptotic Bcl-2 and COX-2 confirmed that the apoptosis induction was via the mitochondria-dependent pathway.

Evaluation of the prevalence of gestational diabetes mellitus in North Indians using the International Association of Diabetes and Pregnancy Study groups (IADPSG) criteria.

OBJECTIVE: Currently, there is controversy regarding the diagnosis of gestational diabetes mellitus (GDM) as per the newer International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. We studied the prevalence and associations of GDM in North Indians, diagnosed by the IADPSG criteria. PATIENTS AND METHODS: We conducted a cross-sectional study on 332 pregnant women, predominantly belonging to lower and middle socioeconomic strata. The women were screened for GDM between 24 weeks and 28 weeks of gestation by 75g oral glucose tolerance test (OGTT) and GDM diagnosed by the IADPSG criteria. RESULTS: The prevalence of GDM was 41.9% [95% Confidence interval (CI) 36.6-47.2%]. Amongst the women diagnosed to have GDM, 91.4% had abnormal fasting plasma glucose (FPG), while 1-h and 2-h post-glucose (PG) levels were abnormal in 18.7% and 17.3% of women, respectively. No maternal factors were significantly associated with GDM. Birth weight of the neonates was similar in women with GDM as compared to those with normal glucose tolerance. In the entire group, fasting glucose levels were associated with the weight of the patient while 1-h PG levels were associated with weight, height, socioeconomic score, and parity. CONCLUSIONS: There is a very high prevalence rate of GDM using the IADPSG criteria in North Indian women of low and middle socioeconomic strata. Further studies are needed to assess the utility of applying these criteria in settings with limited resources.

Prevalence of genetic variants associated with cardiovascular disease risk and drug response in the Southern Indian population of Kerala.

BACKGROUND AND AIM: This study reports the prevalence of five clinically significant variants associated with increased risk of cardiovascular disorders, and variable responses of individuals to commonly prescribed cardiovascular drugs in a South Indian population from the state of Kerala. MATERIALS AND METHODS: Genomic DNA isolated from 100 out-patient samples from Kerala were sequenced to examine the frequency of clinically relevant polymorphisms in the genes MYBPC3 (cardiomyopathy), SLCO1B1 (statin-induced myopathy), CYP2C9, VKORC1 (response to warfarin) and CYP2C19 (response to clopidogrel). RESULTS: Our analyses revealed the frequency of a 25 bp deletion variant of MYBPC3 associated with risk of cardiomyopathy was 7%, and the SLCO1B1 "C" allele associated with risk for statin-induced myopathy was 15% in this sample group. Among the other variants associated with dose-induced toxicity of warfarin, VKORC1 (c.1639G>A), was detected at 22%, while CYP2C9*3 and CYP2C9*2 alleles were present at a frequency of 15% and 3% respectively. Significantly, the tested sample population showed high prevalence (66%) of CYP2C19*2 variant, which determines response to clopidogrel therapy. CONCLUSIONS: We have identified that certain variants associated with cardiovascular disease and related drug response in the five genes, especially those in VKORC1, CYP2C19 and MYBPC3, are highly prevalent in the Kerala population, with almost 2 times higher prevalence of CYP2C19*2 variant compared with other regions in the country. Since the variants chosen in this study have relevance in disease phenotype and/or drug response, and are detected at a higher frequency, this study is likely to encourage clinicians to perform genetic testing before prescribing therapy.

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.

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.

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.

Possible source of intermediate ions over marine environment.

Measurements of small, intermediate and large ions made onboard ORV Sagarkanya over the Arabian Sea in May-June 2003 during Arabian Sea Monsoon Experiment (ARMEX) are reported here. The daily averaged values of small-, intermediate-, and large-ion concentrations measured for 36 days during this cruise have been used for analysis. The analysis shows a weak positive correlation of 0.14 between intermediate- and large-ion concentrations, which indicates that the sources of these two types of ions are different over ocean surface. The negative correlation is observed between small- and intermediate-ion concentration for entire period of cruise. In addition, it is seen that the intermediate-ion concentration shows a very good (r = 0.58) and significant positive correlation with sea surface pressure. Based on good negative correlation between small- and intermediate-ion concentrations and good positive correlation between intermediate-ion concentration and sea surface pressure, it has been proposed that attachment of small ions to the ultrafine particles transported from upper troposphere to marine boundary layer is the main source of intermediate ions over ocean surface. This study supports the idea that the main source of ultrafine particles over marine boundary layer (MBL) is entrainment of aerosol particles from the free troposphere.

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.

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.

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.

Effects of Aroclor 1254 on femoral bone metabolism in adult male Wistar rats.

Environmental pollutants that disrupt endocrine system might also affect the modeling and remodeling of bone. Environmental factors, irrespective of age and sex contribute for the development of secondary osteoporosis. Polychlorinated biphenyls have adverse effects on various organs including bone. The present study was designed to investigate the effects of PCB (Aroclor 1254) on femur bone and the ameliorative role of vitamin C or E. In this regard, four groups of adult male albino rats were used as control, PCB (2mg/kgb.wt.), PCB+vitamin C (100mg/kgb.wt.) and PCB+vitamin E (50mg/kgb.wt.). The bone formation markers (ALP, Collagen), bone resorption marker (TRAP), antioxidant enzymes (SOD, GPX and GST) and lipid peroxidation in the femur were studied. Aroclor 1254 treatment decreased the ALP activity and collagen, but increased the TRAP activity and lipid peroxidation. While it decreased the SOD and GPX activity, GST was unaltered. Interestingly, simultaneous administration of vitamin C or E prevented the adverse effects of Aroclor 1254 in the femur. In conclusion, the present investigation suggests that Aroclor 1254 induced oxidative stress affects femoral bone metabolism. However, vitamin C or vitamin E protected the femur from the oxidative stress.

Microstructure of equilibrium fluid clusters in colloid-polymer suspensions.

Several studies on colloidal depletion systems have reported the existence of a fluid phase consisting of clusters of particles above a critical polymer concentration that acts as a precursor regime to the gel phase at low colloid volume fractions (phi

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.