Sclerotherapy in the Treatment of Hydroceles: A Comprehensive Review of the Efficacy, Types of Sclerosants, and Comparative Outcomes Against Hydrocelectomy.

While hydrocelectomy is the gold-standard for treating hydroceles, it poses an increased risk to patients and a greater burden to the healthcare system. Sclerotherapy is an alternative treatment for hydroceles that involves injecting a sclerosant into the hydrocele under ultrasound guidance. This literature review aimed to assess the types of sclerosants used and how sclerotherapy compares to hydrocelectomy. A literature search was conducted of MEDLINE and EMBASE using the terms "sclerotherapy" and "hydrocelectomy," which yielded 1058 studies, of which 29 met the inclusion criteria. Only studies published after 2000 were included to ensure the most recent information was reviewed. The results showed hydrocele sclerotherapy is done using a variety of sclerosants. The most used agents are polidocanol, phenol, and STS. Of these, phenol had the highest clinical success rate of 96.5%. There was evidence for the use of atypical agents, such as tetracycline antibiotics, which yielded cure rates up to 93%, and alcohol, which was found to be especially useful for treating multiseptated hydroceles. The results comparing sclerotherapy to hydrocelectomy indicated hydrocelectomy to be a more effective method in completely curing hydroceles. However, this came at the cost of more complications. Additionally, sclerotherapy was found to be more advantageous for secondary outcomes, such as healthcare costs and burden to patients. In conclusion, this review shows that while hydrocelectomy is more effective, sclerotherapy is a valuable alternative for treating hydroceles. Due to the lack of standardization among studies, a definitive conclusion cannot be made regarding which sclerosant is best to use.

GIS based hotspot analysis and health risk assessment of groundwater arsenic from an unconfined deep aquifer of Lahore, Pakistan.

Use of groundwater for drinking purpose poses serious hazards of arsenic contamination particularly in plains of western Himalayan region. Therefore, current study was designed to investigate the level of Arsenic (As) in the water obtained from tubewells in a metropolitan city of Lahore, Pakistan and assess the human health risk. So, a total of 73 tubewells were sampled randomly in the manner that the whole study region was covered without any clustering. The water samples were analyzed for As using atomic absorption spectrophotometer. These samples were also tested for total dissolved solids, chlorides, pH, alkalinity, turbidity, hardness and calcium. GIS based hotspots analysis technique was used to investigate the spatial distribution patterns. Our results revealed that only one sample out of total 73 had arsenic level below the WHO guideline of 10 µg/L. The spatial distribution map of arsenic revealed that the higher concentrations of arsenic are present in the north-western region of Lahore. The cluster and outlier analysis map using Anselin Local Moran's I statistic indicated the presence of an arsenic cluster in the west of River Ravi. Furthermore, the optimized hotspot analysis based on Getis-Ord Gi* statistics confirmed the statistical significance (P < 0.05) and (P < 0.01) of these samples from the vicinity of River Ravi. Regression analysis showed that variables such as turbidity, alkalinity, hardness, chlorides, calcium and total dissolved solids were significantly (all P < 0.05) associated with level of Arsenic in tubewells. Whereas, PH and electrical conductivity and other variables like town, year of installation, depth and diameter of the wells were not significantly associated with Arsenic concentrations in tubewells. Principal component analysis (PCA) exhibited that the random distribution of tubewell samples showed no distinct clustering with towns studied. Health risk assessment based on hazard and Cancer risk index revealed serious risk of developing carcinogenic and non-carcinogenic diseases particularly in children. The health risk due to prevalence of high As concentration in tubewells' water need to be mitigated immediately to avoid worst consequences in future.

Trends and projections of land use land cover and land surface temperature using an integrated weighted evidence-cellular automata (WE-CA) model.

Land use land cover (LULC) change has become a major concern for biodiversity, ecosystem alteration, and modifying the climatic pattern especially land surface temperature (LST). The present study assessed past and predicted future LULC and LST change in the Swabi District of Pakistan. LULC maps were generated from satellite data for years 1987, 2002, and 2017 using supervised classification. Mean LST and its areal change were estimated for different LULC classes from thermal bands of satellite images. LULC and LST were projected for the year 2047 using the integrated weighted evidence-cellular automata (WE-CA) model and a regression equation developed in this study, respectively. LULC change revealed an increase of > 5% in the built-up while a decrease in the agricultural area by ~ 9%. There was an increase of ~ 63% area in the LST class ≥ 27 °C which may create urban heat island (UHI). Simulation results indicated that the built-up area will further be increased by ~ 3% until 2047. Area associated with LST class > 30 °C indicated a further increase of ~ 38% till 2047 with reference to year 2017. Findings of this study suggested proper utilization of LULC in order to mitigate the creation of UHIs associated with urbanization and built-up areas.

Immunoinformatics approaches to explore B and T cell epitope-based vaccine designing for SARS-CoV-2 Virus.

SARS-CoV-2, a new world coronavirus belonging to class Nidovirales of Coronaviridae family causes COVID-19 infection which is the leading cause of death worldwide. Currently there are no approved drugs and vaccines available for the prevention of COVID-19 infection, although couples of immunizations are being tested in clinical trials. However, the present efforts are focused on computational vaccination technique for evaluating candidates to design multi-epitope-based vaccine against pathogenic mechanism of novel SARS-COV-2. Based on recent published evidence, we recognized spike glycoprotein and envelope small membrane protein are the potential targets to combat the pathogenic mechanism of SARS-CoV-2. Similarly, in the present study we identified epitope of both B and T cell associated with these proteins. Extremely antigenic, conserve, immunogenic and nontoxic epitope of B and T cell of Spike protein are WPWYVWLGFI, SRVKNLNSSEGVPDLLV whereas the CWCARPTCIK and YCCNIVNVSL are associated with envelope small membrane protein were selected as potential candidate for vaccine designing. These epitopes show virtuous interaction with HLAA0201 during molecular docking analysis. Under simulation protocol the predicted vaccine candidates show stability. Collectively, this work provides novel potential candidates for epitope-based vaccine designing against COVID-19 infection.

Genome wide association study and phylogenetic analysis of novel SARS-COV-2 virus among different countries.

Corona Virus (COVID-19) outbreak has threatened the world, since it has become pandemic and spread all over the world. The causative agent SARS-COV2 has proved lethal caused serious public health concern worldwide. Our aims were to describe the SARS-COV-2 genetic connections and check for recombination of all genome. The recombination was investigated by RDP5 and conflicting phylogenetic clustering in individual genomic fragments was established by phylogenetic study by maximum likelihood and Bayesian methods. Our analysis suggests that the available sequences from currently genomes of various strain were retrieved from different countries including Japan, French Republic, Spain, Peru, China, Vietnam, Taiwan, Brazil, U.S.A., South Korea, Sweden, Australia, Nepal, India, Iran, and Italy. The phylogeny of SARS-COV-2 observed the largest number of genome is Vietnam 29891-bp, while France is the smallest member identified with 29679-bp. Using Recombination Detection program5 (RDP5) the china strains was taken as parental strain but there were no recombination in the all strains. In our study we identified the mutation in Pakistani strains in high conserved region of Corona nucleoca super family domain at the nucleotide position (394: C replace with T, Position: 858: C replace with T and Position: 997 G replace A).

Use of Oral Vitamin-D Glass ampoule and tablet: Experience of patients and physicians.

OBJECTIVE: To ascertain patients and physician views regarding hazard and compliance of oral liquid Vitamin D glass ampoule and tablets. METHODS: This cross sectional survey was conducted from November 1st 2016 to 15th December 2016. Patients who were prescribed Vitamin D glass ampoule from oral route in last three months were included along with physicians who routinely prescribe vitamin D after taking informed consent. The participants were asked about injuries related to the use of glass ampoule, ease of using this from, after taste preference of tablet or injectable form as well as demography. Data was analysed with SPSS version 24.0. RESULTS: Total 182 patients were included in the study with mean ± SD age of 39.4 ± 12.4 years. Majority of patients, 80.2% (142) said they prefer oral tablet in preference to injectable ampule in oral form if given choice while prescribing Vitamin D. Moreover 66.7% (64) doctors prefer to prescribe tablet form of Vitamin D instead of injection as oral form for vitamin D deficiency among their patients. One third of patients, 33% (n=59) sustained injury while breaking the ampule which included minor self-controlled bleeding by glass particles in 50% (n=35). Less than half of doctors 46.9% (n=45) said they taught their patients about usage of injectable Vitamin D ampules. CONCLUSION: Majority of patients prefer Vitamin D tablet instead of Oral liquid in glass ampoule if they got the choice among two. The results of this study provide important implications for our doctors about patients concern of hazard, after taste and compliance with orally administered Vitamin D glass ampoules.

ExpR coordinates the expression of symbiotically important, bundle-forming Flp pili with quorum sensing in Sinorhizobium meliloti.

Type IVb pili in enteropathogenic bacteria function as a host colonization factor by mediating tight adherence to host cells, but their role in bacterium-plant symbiosis is currently unknown. The genome of the symbiotic soil bacterium Sinorhizobium meliloti contains two clusters encoding proteins for type IVb pili of the Flp (fimbrial low-molecular-weight protein) subfamily. To establish the role of Flp pili in the symbiotic interaction of S. meliloti and its host, Medicago sativa, we deleted pilA1, which encodes the putative pilin subunit in the chromosomal flp-1 cluster and conducted competitive nodulation assays. The pilA1 deletion strain formed 27% fewer nodules than the wild type. Transmission electron microscopy revealed the presence of bundle-forming pili protruding from the polar and lateral region of S. meliloti wild-type cells. The putative pilus assembly ATPase CpaE1 fused to mCherry showed a predominantly unilateral localization. Transcriptional reporter gene assays demonstrated that expression of pilA1 peaks in early stationary phase and is repressed by the quorum-sensing regulator ExpR, which also controls production of exopolysaccharides and motility. Binding of acyl homoserine lactone-activated ExpR to the pilA1 promoter was confirmed with electrophoretic mobility shift assays. A 17-bp consensus sequence for ExpR binding was identified within the 28-bp protected region by DNase I footprinting analyses. Our results show that Flp pili are important for efficient symbiosis of S. meliloti with its plant host. The temporal inverse regulation of exopolysaccharides and pili by ExpR enables S. meliloti to achieve a coordinated expression of cellular processes during early stages of host interaction.

Groundwater quality assessment and its correlation with gastroenteritis using GIS: a case study of Rawal Town, Rawalpindi, Pakistan.

Majority of the people of Pakistan get drinking water from groundwater source. Nearly 40 % of the total ailments reported in Pakistan are the result of dirty drinking water. Every summer, thousands of patients suffer from acute gastroenteritis in the Rawal Town. Therefore, a study was designed to generate a water quality index map of the Rawal Town and identify the relationship between bacteriological water quality and socio-economic indicators with gastroenteritis in the study area. Water quality and gastroenteritis patient data were collected by surveying the 262 tubewells and the major hospitals in the Rawal Town. The collected spatial data was analyzed by using ArcGIS spatial analyst (Moran's I spatial autocorrelation) and geostatistical analysis tools (inverse distance weighted, radial basis function, kriging, and cokriging). The water quality index (WQI) for the study area was computed using pH, turbidity, total dissolved solids, calcium, hardness, alkalinity, and chloride values of the 262 tubewells. The results of Moran's I spatial autocorrelation showed that the groundwater physicochemical parameters were clustered. Among IDW, radial basis function, and kriging and cokriging interpolation techniques, cokriging showed the lowest root mean square error. Cokriging was used to make the spatial distribution maps of water quality parameters. The WQI results showed that more than half of the tubewells in the Rawal Town were providing "poor" to "unfit" drinking water. The Pearson's coefficient of correlation for gastroenteritis with fecal coliform was found significant (P < 0.05) in Water and Sanitation Agency (WASA) zone 2, and with shortage of toilets, it was significant (P < 0.05) in WASA zones 1 and 3. However, it was significantly (P < 0.01) inversely related with literacy rate in WASA zones 1, 2, and 3.

Loss of prohibitin 2 in Schwann cells dysregulates key transcription factors controlling developmental myelination.

Schwann cells are critical for the proper development and function of the peripheral nervous system, where they form a mutually beneficial relationship with axons. Past studies have highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development. Here, we expand on this work, showing that drug-mediated modulation of prohibitins in vitro disrupts myelination and confirming that Schwann cell-specific ablation of prohibitin 2 (Phb2) in vivo results in early and severe defects in peripheral nerve development. Using a proteomic approach in vitro, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on the presence of axonal signals. Furthermore, we show in vivo that loss of Phb2 in mouse Schwann cells causes ineffective proliferation and dysregulation of transcription factors EGR2 (KROX20), POU3F1 (OCT6) and POU3F2 (BRN2) that are necessary for proper Schwann cell maturation. Schwann cell-specific deletion of Jun, a transcription factor associated with negative regulation of myelination, confers partial rescue of the development defect seen in mice lacking Schwann cell Phb2. This work develops our understanding of Schwann cell biology, revealing that Phb2 may directly or indirectly modulate the timely expression of transcription factors necessary for proper peripheral nervous system development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell.

Nexus among the perceived infrastructural, social, economic, and environmental impact of CPEC: A case of Pakistan.

Despite its ambitious "economic sustainability" objectives, the China-Pakistan Economic Corridor (CPEC) has been the subject of growing environmental anxiety. Considering the CPEC developments, it is clear that Pakistan is ready to fully embrace this new industrial chapter and take advantage of its major benefits to solve social, energy, infrastructure, and economic problems. However, it should also seriously commit to undertaking proper environmental impact assessments and upgrading system resilience. Data was collected from 400 respondents from Pakistan, and structural equation modeling was applied with the help of AMOS. Factor analysis and structural equation modeling techniques were used to estimate the results and test the study's hypothesis. The results indicate a strong socio-economic impact across perceived economic, infrastructure, social, and total impacts, but they identify a negative association between infrastructure innovation and environmental sustainability. Moreover, results revealed that infrastructure supports social and economic growth, but it might have a substantial negative impact on biodiversity. According to findings, Pakistan may be more vulnerable to climate change due to three potential environmental issues: coal-fired power plants, CO2 concentration along the CPEC route, and increased traffic on the Karakorum Highway. Furthermore, future international trade will be significantly impacted by the corridor. It may, however, also accelerate the destruction of the ecosystem over time due to the industrial revolution.

Internet of Things enables smart solid waste bin management system for a sustainable environment.

Solid waste management (SWM) is a pressing concern and significant research topic that requires attention from citizens and government stakeholders. Most of the responsibility of waste management is on the municipal sector for its collection, reallocation, and reuse of other resources. The daily solid waste production is more than 54,850 tonnes in urban areas and is difficult to manage due to limited resources and different administrative and service issues. New technologies are playing their role in this area but how to integrate the technologies is still a question, especially for developing countries. This paper is divided into two main phases including a detailed investigation and a technological solution. In the first phase, the data is collected by using the qualitative method to investigate and identify the issues related to waste management. After a detailed investigation and results, the gap is identified by using statistical analysis and proposed a technological solution in the second phase. The technology-based solution is used to control and manage waste with a low-cost, fast, and manageable solution. The new sensor-based technologies, cellular networks, and social media are utilized to monitor the trash in the areas. The trash management department receives notification via cellular services to locate the dustbin when the dustbin reaches a maximum level so the department may send a waste collector vehicle to the relevant spot to collect waste. The smart and fast solution will connect all stakeholders in the community and reduce the cost and time and make the collection process faster. The experiment results indicated the issues and effectiveness of the proposed solution.

Health risk assessment and geospatial analysis of arsenic contamination in shallow aquifer along Ravi River, Lahore, Pakistan.

The exposure variation of arsenic from different ground and surface water sources has remained unpredictable which may cause severe human health problems. The current study is, therefore, designed to analyze the spatial variability of arsenic contamination in shallow aquifer and assess the potential human health risks. For this purpose, a total of 55 groundwater, 10 drain water, 4 river water, and 6 sediment samples were collected along zero to 5 km stretch of the River Ravi, Lahore. All water samples were tested for As, pH, and total dissolved solids (TDS), whereas sediments were only tested for As. Health risk models were used to predict cancer and non-cancer risk in adults and children. Among water samples, highest median (minimum-maximum) concentrations (µg/L) of As were recorded 53.32 (1.98-1555) in groundwater, followed by 53.04 (1.58-351.5) in drain water, and 4.80 (2.13-8.67) in river water, respectively, whereas As concentration (mg/kg) in river sediments was 6.03 (5.56-13.92). Variation of As in groundwater was non-significant (P > 0.05) among every 1-km stretch from the Ravi River. However, maximum median concentrations (µg/L) of 60.18 and 60.08 were recorded between 2-3 and 0-1 km from River Ravi, respectively, reflecting possible mixing of river water with shallow aquifers. A very high cancer and non-cancer risk (HI > 1.0 × 10-4) through groundwater As exposure was predicted for both children and adults. The current study concluded that prevalence of As above WHO prescribed limits in shallow aquifer along the urban stretch of the River Ravi is posing serious health risk to the exposed population.

Computational screening and analysis of deleterious nsSNPs in human p14ARF (CDKN2A gene) protein using molecular dynamic simulation approach.

Cyclin-dependent kinase inhibitor 2 A (CDKN2A) gene belongs to the cyclin-dependent kinase family that code for two transcripts (p16INK4A and p14ARF), both work as tumor suppressors proteins. The mutation that occurs in the p14ARF protein can lead to different types of cancers. Single nucleotide polymorphisms (SNPs) are an important type of genetic alteration that can lead to different types of diseases. In this study, we applied the computational strategy on human p14ARF protein to identify the potential deleterious nsSNPs and check their impact on the structure, function, and protein stability. We applied more than ten prediction tools to screen the retrieved 288 nsSNPs, consequently extracting four deleterious nsSNPs i.e., rs139725688 (R10G), rs139725688 (R21W), rs374360796 (F23L) and rs747717236 (L124R). Homology modeling, conservation and conformational analysis of mutant models were performed to examine the divergence of these variants from the native p14ARF structure. All-atom molecular dynamics simulation revealed a significant impact of these mutations on protein stability, compactness, globularity, solvent accessibility and secondary structure elements. Protein-protein interactions indicated that p14ARF operates as a hub linking clusters of different proteins and that changes in p14ARF may result in the disassociation of numerous signal cascades. Our current study is the first survey of computational analysis on p14ARF protein that determines the association of these nsSNPs with the altered function of p14ARF protein and leads to the development of various types of cancers. This research proposes the described functional SNPs as possible targets for proteomic investigations, diagnostic procedures, and treatments.Communicated by Ramaswamy H. Sarma.

In silico scanning of structural and functional deleterious nsSNPs in Arabidopsis thaliana's SOG1 protein, using molecular dynamic simulation approaches.

Suppressor of gamma response 1 (SOG1) is a member of the NAC domain family transcription factors of the DNA damage response (DDR) signaling in the plant's genome. SOG1 is directly involved in transcriptional response to DNA damage, cell cycle checkpoints and ATR or ATM-mediated activation of the DNA damage responses and repair functioning in programmed cell death and regulation of end reduplication. Different mutations in the SOG1 protein lead to severe diseases and, ultimately, cell death. Single nucleotide polymorphisms (SNPs) are an important type of genetic alteration that cause different diseases or programmed cell death. The current study applied different computational approaches to Arabidopsis thaliana L. SOG1 protein to identify the potential deleterious nsSNPs and monitor their impact on the structure, function and protein stability. Various bioinformatics tools were applied to analyze the retrieved 34 nsSNPs and interestingly extracted four deleterious nsSNPs, that is, ensvath13968004 (Q166L), tmp18998388 (P159L), ensvath01103049 (K199N) and tmp18998295 (Y190F). For example, homology modeling, conservation and conformational analysis of the mutant's models were considered to scrutinize the deviations of these variants from the native SOG1 structure. All atoms molecular dynamic simulation confirmed the significance of these mutations on the protein stability, residual and structural conformation, compactness, surface conformation, dominant motion, Gibbs free energy distribution and dynamic effects. Similarly, protein-protein interaction revealed that SOG1 operates as a hub-linking cluster of various proteins, and any changes in the SOG1 might result in the disassociation of several signal transduction cascades.Communicated by Ramaswamy H. Sarma.

Minimally invasive delivery of ethanol for the treatment of urinary bladder fistulas.

Urinary bladder fistula formation is a complication of significant morbidity and mortality following pelvic surgery or radiotherapy. Surgical treatment is the definitive management, but it may be contraindicated in patients with significant comorbidities. The alternative approach is to divert urine away from the fistula with stents and catheters, and allow time for healing. The case illustrated herein describes the use of alcohol to accelerate the fibrotic healing of a urinary bladder fistula, based on the premise that sclerosing agents have been effective in the treatment of pancreatic fistulas and renal cysts. A Foley catheter is inserted through the external fistula orifice and passed along the fistula tract into the urinary bladder. The Foley catheter balloon is inflated and pulled back to occlude the fistula. Following this, a vascular sheath is placed alongside the catheter and ethanol is injected into the tract. The alcohol is left to dwell in the fistula for a few minutes, after which time the catheter and sheath are removed. The sclerosant effect of the ethanol aims to induce fibrosis, and therefore occlusion, of the fistula.

A multi-tissue biomonitoring investigation of toxic trace elements and their trophic transfer potential in a semi aquatic bird species, the Cattle Egret (Bubulcus ibis).

The constant exposure of toxic trace elements can elicit adverse health effects particularly in birds and species residing higher at the food web. The current study is designed to evaluate the tendency of toxic trace elements viz. Cd, Cr, Pb, Cu, As and Hg to bioaccumulate in liver, kidney, blood, pelvic and pectoral muscles of cattle egret (Bubulcus ibis) collected from premises of a metropolitan city, Lahore, Pakistan. Further, the Trophic Transfer Potential of these elements was also estimated using prey/food samples of cattle egret. All of the selected toxic trace elements except Hg and As were detected with varying concentrations in different tissues of cattle egret. In general, toxic trace elements followed the pattern as Cu > Pb > Cd > Cr in tissues of cattle egret. The maximum mean (Min-max) concentrations (µg/g) of Cu 0.58 (0.11-0.93) and Pb 0.46 (0.40-0.54) in blood and Cd at 0.46 (0.40-0.54) were observed in liver. Similarly, the highest mean (min-max) concentration (µg/g) of Cr 0.17 (0.09-0.25) was recorded in pectoral muscle. In general, blood and liver were found as the most contaminated tissues followed by kidney, pectoral and pelvic muscles. Differences of trace elements were found non-significant (all P > 0.05) among tissues of cattle egret reflecting their homogenous distribution in body. Principal Component Analysis (PCA) corroborated lack of strong association between any of the trace elements and tissues. All the toxic trace elements except Cr showed higher tendency of trophic transfer potential through food chain in all the tissues of Cattle Egret (TTF >1). Although the current study revealed decreasing trends of toxic trace elements, yet their still presence in the local environment and greater likelihood of trophic transfer can undoubtedly cause some severe health effects to the already declining bird populations.

Structural, genomic information and computational analysis of emerging coronavirus (SARS-CoV-2).

Background: The emerging viral pandemic worldwide is associated with a novel coronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). This virus is said to emerge from its epidemic center in Wuhan, China, in 2019. Coronaviruses (CoVs) are single-stranded, giant, enveloped RNA viruses that come under the family of coronaviridae and order Nidovirales which are the crucial pathogens for humans and other vertebrates. Main body: Coronaviruses are divided into several subfamilies and genera based on the genomic structure and phylogenetic relationship. The name corona is raised due to the presence of spike protein on the envelope of the virus. The structural and genomic study revealed that the total genome size of SARS-CoV-2 is from 29.8 kb to 29.9 kb. The spike protein (S) is a glycoprotein that attaches to the receptor of host cells for entry into the host cell, followed by the attachment of virus RNA to the host ribosome for translation. The phylogenetic analysis of SARS-CoV-2 revealed the similarity (75-88%) with bat SARS-like coronavirus. Conclusion: The sign and symptoms of novel severe acute respiratory syndrome coronavirus 2 are also discussed in this paper. The worldwide outbreak and prevention from severe acute respiratory syndrome coronavirus 2 are overviewed in the present article. The latest variant of coronavirus and the status of vaccines are also overviewed in the present article.

A comprehensive genomic study, mutation screening, phylogenetic and statistical analysis of SARS-CoV-2 and its variant omicron among different countries.

BACKGROUND: With the rapid development of the genomic sequence data for the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants Delta (B.1.617.2) and Omicron (B.1.1.529), it is vital to successfully identify mutations within the genome. OBJECTIVE: The main objective of the study is to investigate the full-length genome mutation analysis of 157 SARS-CoV-2 and its variant Delta and Omicron isolates. This study also provides possible effects at the structural level to understand the role of mutations and new insights into the evolution of COVID-19 and evaluates the differential level analysis in viral genome sequence among different nations. We have also tried to offer a mutation snapshot for these differences that could help in vaccine formulation. This study utilizes a unique and efficient method of targeting the stable genes for the drug discovery approach. METHODS: Complete genome sequence information of SARS-CoV-2, Delta, and Omicron from online resources were used to predict structure domain identification, data mining, and screening; employing different bioinformatics tools. BioEdit software was used to perform their genomic alignments across countries and a phylogenetic tree as per the confidence of 500 bootstrapping values was constructed. Heterozygosity ratios were determined in-silico. A minimum spanning network (MSN) of selected populations was determined by Bruvo's distance role-based framework. RESULTS: Out of all 157 different strains of SARS-CoV-2 and its variants, and their complete genome sequences from different countries, Corona nucleoca and DUF5515 were observed to be the most conserved domains. All genomes obtained changes in comparison to the Wuhan-Hu-1 strain, mainly in the TRS region (CUAAAC or ACGAAC). We discovered 596 mutations in all genes, with the highest number (321) found in ORF1ab (QHD43415.1), or TRS site mutations found only in ORF7a (1) and ORF10 (2). The Omicron variant has 30 mutations in the Spike protein and has a higher alpha-helix shape (23.46%) than the Delta version (22.03%). T478 was also discovered to be a prevalent polymorphism in Delta and Omicron variations, as well as genomic gaps ranging from 45 to 65aa. All 157 sequences contained variations and conformed to Nei's Genetic distance. We discovered heterozygosity (Hs) 0.01, mean anticipated Hs 0.32, the genetic diversity index (GDI) 0.01943989, and GD within population 0.01266951. The Hedrick value was 0.52324978, the GD coefficient was 0.52324978, the average Hs was 0.01371452, and the GD coefficient was 0.52324978. Among other countries, Brazil has the highest standard error (SE) rate (1.398), whereas Japan has the highest ratio of Nei's gene diversity (0.01). CONCLUSIONS: The study's findings will assist in comprehending the shape and kind of complete genome, their streaming genomic sequences, and mutations in various additions of SARS-CoV-2, as well as its different variant strains like Omicron. These results will provide a scientific basis to design the vaccines and understand the genomic study of these viruses.

In Silico and In Vitro Screening Constituents of Eclipta alba Leaf Extract to Reveal Antimicrobial Potential.

Phytochemicals have been shown to possess multiple bioactives and have been reported to showcase many medicinal effects. A similar kind of evaluation of phytoconstituents for their antimicrobial action has been reported, based on in vitro and in silico data. The goal of the research was to explore bioactive phytoconstituents of Eclipta alba leaf for antimicrobial activity. The antimicrobial activity was validated by both molecular docking and antimicrobial assay. Bioactive metabolites were identified using GC-MS. The antimicrobial and antimycobacterial activity of Eclipta alba leaves was investigated using the Kirby-Bauer well diffusion method and the rapid culture-MGIT™ DST method against a variety of human pathogens, as well as Mycobacterium tuberculosis (H37Rv) and Mycobacterium tuberculosis bacteria resistant to isoniazid and rifampicin. Eclipta alba's GC-MS studies confirmed the detection of 17 bioactive constituents. The extract demonstrates the highest antibacterial activity against Escherichia coli (sensitive), Pseudomonas aeruginosa (sensitive) and methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa susceptible and MRSA (sensitive) with zone of inhibition of 27 mm, 24 mm, and 32 mm respectively. The extract showed no effect on Mycobacterium tuberculosis (H37Rv) and Mycobacterium tuberculosis bacteria resistant to isoniazid and rifampicin in antimycobacterial activity testing. Molecular docking investigation revealed that three compounds (phthalic acid, isobutyl octadecyl ester, hexadecanoic acid, 1(hydroxymethyl)1,2-ethanediylester, and 2,myristynoyl pantetheine) have generated the best results in terms of binding energies and significant interactions with key residues of target protein 3-hydroxydecanoyl-acyl carrier protein dehydratase (FabA) and confirm its activity as antimicrobial inhibitors. These two-dimensional plots show significant protein-ligand binding interactions (van der Waals interactions, hydrogen bond, alkyl, and Pi-alkyl interactions). ADMET (absorption, distribution, metabolism, excretion, and toxicity) results additionally support the drug-likeness characteristics of concluded potential compounds. The experimental and computational results demonstrated that methanolic extract of Eclipta alba leaves had antimicrobial effects for specific infections due to the presence of phytochemical compounds.

Modern drug discovery applications for the identification of novel candidates for COVID-19 infections.

In early December 2019, a large pneumonia epidemic occurred in Wuhan, China. The World Health Organization is concerned about the outbreak of another coronavirus with the powerful, rapid, and contagious transmission. Anyone with minor symptoms like fever and cough or travel history to contaminated places might be suspected of having COVID-19. COVID-19 therapy focuses on treating the disease's symptoms. So far, no such therapeutic molecule has been shown effective in treating this condition. So the treatment is mostly supportive and plasma. Globally, numerous studies and researchers have recently started fighting this virus. Vaccines and chemical compounds are also being investigated against infection. COVID-19 was successfully diagnosed using RNA detection and very sensitive RT-PCR (reverse transcription-polymerase chain reaction). The evolution of particular vaccinations is required to reduce illness severity and spread. Numerous computational analyses and molecular docking have predicted various target compounds that might stop this condition. This paper examines the main characteristics of coronavirus and the computational analyses necessary to avoid infection.