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While pilots and production use of software based on the Health Level Seven (HL7®) Fast Healthcare Interoperability Resources (FHIR®) standard are increasing in clinical research, we lack consistent evaluative data on important outcomes, such as data accuracy. We compared the accuracy of EHR collected, FHIR® extracted data (called EHR-to-eCRF data collection) to traditional clinical trial data collection. The accuracy rate for EHR-collected data was significantly higher than for the same data collected through traditional methods. It is possible that EHR-collected (FHIR® extracted) data can substantially improve data quality in clinical studies while decreasing the burden on study sites.
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Ensayos Clínicos como Asunto , Registros Electrónicos de Salud , Interoperabilidad de la Información en Salud , Humanos , Exactitud de los Datos , Estándar HL7RESUMEN
Glioblastoma multiforme (GBM) is a highly severe primary brain tumor. Despite extensive research, effective treatments remain elusive. Long noncoding RNAs (lncRNAs) play a significant role in both cancer and normal biology. They influence alternative splicing (AS), which is crucial in cancer. Advances in lncRNA-specific microarrays and next-generation sequencing have enhanced understanding of AS. Abnormal AS contributes to cancer invasion, metastasis, apoptosis, therapeutic resistance, and tumor development, including glioma. lncRNA-mediated AS affects several cellular signaling pathways, promoting or suppressing cancer malignancy. This review discusses the lncRNAs regulating AS in glioblastoma and their mechanisms.
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Background: Irrespective of the availability of a safe and effective COVID-19 vaccine and its success rate in adults, administering vaccines to children remains a challenge for healthcare workers. Children's vaccine hesitancy among parents remains substantial and is exacerbated due to misleading information. In the present study, we aimed to investigate the hesitancy of parents and their concern about the vaccination and clinical characteristics of COVID-19 in their children. Methods: A cross-sectional web-based and offline survey comprised of questions about the demographic of children, the status of COVID-19 infection, its severity, vaccination status, sources of information, willingness, concerns and attitude of parents to vaccinate their children against the COVID-19 virus, was conducted. Overall, 846 responses from parents fulfilling the inclusion criteria were analysed by GraphPad Prism 5. Results: Out of the 846 responses, 51.2% (n = 433) of children were vaccinated against COVID-19. Out of vaccinated children (51.2%), 60.3% (n = 261) had experienced adverse events. Around 21% (n = 98) of children had a history of exposure to the SARS-CoV-2 virus. Among the infected children, 14.3% were asymptomatic and 85.7% had symptoms. Approximately 8% of children had comorbidities, with chronic lung diseases and asthma being the most common. Among the 846 participating parents, 59.5% were mothers and the remaining 40.5% were fathers. A total of 2.7% and 22.2% of parents were found hesitant to administer the COVID-19 vaccine to their children aged 15-18 years and below 15 years, respectively. Among hesitant parents, mothers were found slightly more hesitant as compared to fathers. Also, 35.5% of parents were found hesitant about their own COVID-19 vaccination. Furthermore, the concern for COVID-19 vaccine unwillingness among parents is that a child has already achieved natural immunity after COVID-19 infections (76.8%) followed by vaccine safety and its side effects. The motivating factors to convince parents for their children's COVID-19 vaccination were if their doctors recommend it, followed by detailed information on vaccine side effects and efficacy in children. The most trusted source of information for the parents was found to be the healthcare workers. Conclusion: These results suggest that data and reviews regarding the safety and efficacy of the COVID-19 vaccine readily available in the public domain could serve as a highly effective strategy for promoting and implementing widespread vaccination among children. By providing easily accessible and comprehensive information, public health authorities can address parental concerns, dispel misconceptions and foster a greater sense of trust in the vaccination process.
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Intracellular microorganisms, like viruses, bacteria, and fungi, pose challenges in detection due to their non-culturable forms. Transcriptomic analysis at cellular level enables exploration of distributions and the impact of these microorganisms on host cells, a domain that remains underexplored because of methodological limitations. Single-cell technology shows promise in addressing this by capturing polyadenine-tailed transcripts, because recent studies confirmed polyadenylation in microbial transcriptomes. We utilized single-cell RNA-seq from PBMCs to probe intracellular microbes in healthy, SARS-CoV-2-positive, and recovered individuals. Among 76 bacterial species detected, 16 showed significant abundance differences. Buchnera aphidicola, Streptomyces clavuligerus, and Ehrlichia canis emerged significantly in memory-B, Naïve-T, and Treg cells. Staphylococcus aureus, Mycoplasma mycoides, Leptospira interrogans, and others displayed elevated levels in SARS-CoV-2-positive patients, suggesting possible disease association. This highlights the strength of single-cell technology in revealing potential microorganism's cell-specific functions. Further research is essential for functional understanding of their cell-specific abundance across physiological states.
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Malaria and concurrent bacteraemia cases have been reported globally, mostly in association with Plasmodium falciparum malaria. In comparison, concurrent bacteraemia with Plasmodium vivax infected patients is reported rarely. However, considering unavailability of blood culture testing and widespread community and empirical antibiotic usage in low- and middle-income countries (LMICs), the frequency of bacteraemia and P. vivax co-infection may be much higher. We reported two cases of Staphylococcus aureus bacteraemia with P. vivax malaria infection. Both patients presented with high grade fever and chills with unremarkable systemic examination. Liver enzymes were raised along with inflammatory markers. Simultaneous diagnosis of methicillin sensitive S. aureus bacteraemia was done using automated blood culture, automated identification and sensitivity testing system. P. vivax malaria was confirmed with microscopy, antigen detection test and molecular test. Patients recovered uneventfully with antimalarial drugs and antibiotics.
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Bacteriemia , Malaria Falciparum , Malaria Vivax , Malaria , Infecciones Estafilocócicas , Humanos , Malaria Vivax/complicaciones , Malaria Vivax/diagnóstico , Malaria Vivax/tratamiento farmacológico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Bacteriemia/complicaciones , Plasmodium falciparum , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/complicaciones , Staphylococcus aureus , Malaria/complicaciones , Malaria Falciparum/diagnóstico , Plasmodium vivax , IndiaRESUMEN
The milk, meat, skins, and draft power of domestic water buffalo (Bubalus bubalis) provide substantial contributions to the global agricultural economy. The world's water buffalo population is primarily found in Asia, and the buffalo supports more people per capita than any other livestock species. For evaluating the workflow, output rate, and completeness of transcriptome assemblies within and between reference-free (RF) de novo transcriptome and reference-based (RB) datasets, abundant bioinformatics studies have been carried out to date. However, comprehensive documentation of the degree of consistency and variability of the data produced by comparing gene expression levels using these two separate techniques is lacking. In the present study, we assessed the variations in the number of differentially expressed genes (DEGs) attained with RF and RB approaches. In light of this, we conducted a study to identify, annotate, and analyze the genes associated with four economically important traits of buffalo, viz., milk volume, age at first calving, post-partum cyclicity, and feed conversion efficiency. A total of 14,201 and 279 DEGs were identified in RF and RB assemblies. Gene ontology (GO) terms associated with the identified genes were allocated to traits under study. Identified genes improve the knowledge of the underlying mechanism of trait expression in water buffalo which may support improved breeding plans for higher productivity. The empirical findings of this study using RNA-seq data-based assembly may improve the understanding of genetic diversity in relation to buffalo productivity and provide important contributions to answer biological issues regarding the transcriptome of non-model organisms.
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Drug discovery is an extensive process. From identifying lead compounds to approval for clinical application, it goes through a sequence of labor-intensive in vitro, in vivo preclinical screening and clinical trials. Among thousands of drugs screened only a few get approval for clinical trials. Furthermore, these approved drugs are often discontinued due to systemic toxicity and comorbidity at clinically administered dosages. To overcome these limitations, nanoformulations have emerged as the most sought-after strategy to safely and effectively deliver drugs within tumors at therapeutic concentrations. Most importantly, the employment of suitably variable preclinical models is considered highly critical for the therapeutic evaluation of candidate drugs or their formulations. A review of literature from the past 10 years on antiangiogenic nanoformulations shows the employment of limited types of preclinical models mainly the 2-dimensional (2D) monolayer cell culture and murine models as the mainstay for drug uptake, toxicity and efficiency studies. To top it all, murine models are highly expensive, time-consuming and require expertise in handling them. The current review highlights the utilization of the age-old chicken chorioallantoic membrane (CAM), a well-defined angiogenic model in the investigation of antiangiogenic compounds and nanoformulations in an economic framework. For practical applicability, we have evaluated the CAM model to demonstrate the screening of antiangiogenic compounds and that tumor cells can be implanted onto developing CAM for growing xenografts by recruiting host endothelial and other cellular components. In addition, the exploitation of CAM tumor xenograft models for the evaluation of nanoparticle distribution has also been reinforced by demonstrating that intravenously administered iron oxide nanoparticles (IONPs) passively accumulate and exhibit intracellular as well as extracellular compartment accumulation in highly vascular xenografts. Finally, the ethical considerations, benefits, and drawbacks, of using CAM as an experimental model for testing potential therapeutics are also highlighted.
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Pollos , Neoplasias , Humanos , Animales , Ratones , Membrana Corioalantoides/irrigación sanguínea , Membrana Corioalantoides/metabolismo , Neoplasias/metabolismo , Técnicas de Cultivo de CélulaRESUMEN
White mold commonly known as Sclerotinia sclerotiorum causes stem rot disease and has emerged as one of the major fungal pathogens of oilseed Brassica across the world. In the present study, consistently virulent S. sclerotiorum isolate "ESR-01" was sequenced and an assembly size of ~ 41 Mb with 328 scaffolds having N50 of 447,128 was obtained. Additionally, 27,450 single nucleotide polymorphisms (SNPs) were identified from 155 scaffolds against S. sclerotiorum 1980 isolate, with an average SNP density of ~ 1.5 per kb genome. 667 repetitive elements were identified and approximately comprised 7% of the total annotated genes. The DDE_1 with 454 in numbers was found to be the most abundant and accounts for 68% of the total predicted repetitive elements. In total, 3844 simple sequence repeats are identified in the 328 scaffolds. A total of 9469 protein-coding genes were predicted from the whole genome assembly with an average gene length of 1587 bp and their distribution as 230.95 genes per Mb in the genome. Out of 9469 predicted protein-coding genes, 529 genes were observed encoding the CAZymes (Carbohydrate-Active enzymes) capable of degradation of the complex polysaccharides. Glycosyltransferase (GT) families were most abundant (49.71%) among the predicted CAZymes and GT2 (23%), GT4 (20%), and glycoside hydrolase (GH) 23% with GH18 (11%) were the prominent cell wall degrading enzyme families in the ESR-01 secretome. Besides this, 156 genes essential for the pathogen-host interactions were also identified. The effector analysis in the whole genome proteomics dataset revealed a total of 57 effector candidates (ECs) and 27 of them were having their analogs whereas the remaining 30 were novel ones. Eleven selected ECs were validated experimentally by analyzing the expression profile of the ESR-01 isolate of S. sclerotiorum. Together, the present investigation offers a better understanding of the S. sclerotiorum genome, secretome, and its effector repertoire which will help in refining the present knowledge on S. sclerotiorum-Brassica interactions and necrotrophic lifestyle of the phytopathogen in general.
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Ascomicetos , Brassica , Especificidad del Huésped , Secretoma , Mapeo Cromosómico , Brassica/genética , Enfermedades de las Plantas/microbiologíaRESUMEN
SARS-CoV-2 virus pathogenicity and transmissibility are correlated with the mutations acquired over time, giving rise to variants of concern (VOCs). Mutations can significantly influence the genetic make-up of the virus. Herein, we analyzed the SARS-CoV-2 genomes and sub-genomic nucleotide composition in relation to the mutation rate. Nucleotide percentage distributions of 1397 in-house-sequenced SARS-CoV-2 genomes were enumerated, and comparative analyses (i) within the VOCs and of (ii) recovered and mortality patients were performed. Fisher's test was carried out to highlight the significant mutations, followed by RNA secondary structure prediction and protein modeling for their functional impacts. Subsequently, a uniform dinucleotide composition of AT and GC was found across study cohorts. Notably, the N gene was observed to have a high GC percentage coupled with a relatively higher mutation rate. Functional analysis demonstrated the N gene mutations, C29144T and G29332T, to induce structural changes at the RNA level. Protein secondary structure prediction with N gene missense mutations revealed a differential composition of alpha helices, beta sheets, and coils, whereas the tertiary structure displayed no significant changes. Additionally, the N gene CTD region displayed no mutations. The analysis highlighted the importance of N protein in viral evolution with CTD as a possible target for antiviral drugs.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Tasa de Mutación , Nucleótidos , Genoma Viral , ARNRESUMEN
BACKGROUND: Endometrioid endometrial carcinoma (EEC) is the most common invasive malignancy of the female genital tract. Despite advances in diagnosis and treatment, the incidence of EEC and mortality related to it have not decreased. Therefore, research is needed to explore the underlying molecular mechanisms of EEC and its precursors to reduce the mortality and societal burden associated with them. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene most commonly altered in endometrial carcinoma and its precursor lesions. Promoter methylation is a common mechanism for the inactivation of the PTEN tumor suppressor gene. METHODS: This was a prospective nested case-control study involving women aged 35 to 70 years old whose endometrial biopsy and resected samples were obtained for histological diagnosis. Before enrolling a person in the study, signed informed consent was obtained from each individual. The ethics committee for the institute gave its approval to the study protocol. Immunohistochemistry (IHC) was used to measure PTEN expression was measured, and methylation-specific PCR (MSP) was used to determine PTEN promoter methylation status (Bisulfite conversion). RESULTS: A total of 95 samples were assessed histopathologically, along withPTEN expression and PTEN promoter methylation status. PTEN immunoreactivity was observed in 79% (15/19) of normal proliferative endometrium, and loss of PTEN expression was observed in 73% (27/37) of endometrial hyperplasia with or without atypia and 90% (35/39) of EEC. Methylation analysis showed that the PTEN promoter was completely unmethylated in all normal proliferative endometria and endometrial hyperplasia without atypia. In contrast, the promoter region was methylated in 50% of endometrial hyperplasia with atypia cases and 38.5% of EEC cases. CONCLUSION: The loss ofPTEN expression was significantly associated with EEC and precancerous lesions of the endometrium compared to normal proliferative endometria. Methylation analysis also revealed that the frequency of methylation is significant in EEC and endometrial hyperplasia with atypia. Integration of PTEN protein expression along with promoter methylation status elucidates the underlying carcinogenic mechanism. This may help with personalized therapy for EECs and triaging cases of potential precancerous lesions.
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A total of six vegetables (S. tuberosum, D. carota, S. lycopersicum, A. esculentus, S. oleracea and B. juncea) were analysed for five heavy metals (As, Cd, Cr, Hg, and Pb) to evaluate the contamination load in vegetables collected from five cultivated and two market sites (n = 504) at Delhi, India. The irrigation water samples and soil samples (n = 180) were only collected from cultivated sites. The results showed that the concentration of heavy metals in soil and water samples were well below the permissible level except for Cd 0.001-0.013 µg g-1. Similarly, the concentration of Cd (>0.20 µg g-1) was detected higher in all investigated vegetables except for tomato. The evaluation index value was highest for spinach and lowest for tomato. The transfer factor values and metal pollution index was maximum in spinach and okra. Principal component analysis (PCA), Tukey's HSD (Honestly Significant Difference) test, and one-way and two-way ANOVA (Analysis of Variance) were also applied to statistically analyse the results.
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Metales Pesados , Contaminantes del Suelo , Cadmio/análisis , Monitoreo del Ambiente/métodos , Contaminación de Alimentos/análisis , India , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisis , Contaminantes del Suelo/toxicidad , Spinacia oleracea , Verduras , AguaRESUMEN
Vaccines against COVID-19 provide immunity to deter severe morbidities associated with the infection. However, it does not prevent infection altogether in all exposed individuals. Furthermore, emerging variants of SARS-CoV-2 impose a threat concerning the competency of the vaccines in combating the infection. This study aims to determine the variability in adverse events and the extent of breakthrough infections in the Indian population. A retrospective study was conducted using a pre-validated questionnaire encompassing social, demographic, general health, the status of SARS-CoV-2 infection, vaccination, associated adverse events, and breakthrough infections in the Indian population. Informed consent and ethical approval were obtained as per Indian Council of Medical Research (ICMR) guidelines. Participants, who provided the complete information, were Indian citizens, above 18 years, and if vaccinated, administered with either Covishield or Covaxin, were considered for the study. Data have been compiled in Microsoft Excel and analyzed for statistical differences using STATA 11. The responses from 2051 individuals fulfilling the inclusion criteria were analyzed. Among 2051, 1119 respondents were vaccinated and 932 respondents were non-vaccinated. Among 1119 vaccinated respondents, 7 were excluded because of missing data. Therefore, out of 1112 vaccinated, 413 experienced adverse events with a major fraction of younger individuals, age 18-40 years, getting affected (74.82%; 309/413). Furthermore, considerably more females than males encountered adverse consequences to vaccination (p < 0.05). Among vaccinated participants, breakthrough infections were observed in 7.91% (88/1112; 57.96% males and 42.04% females) with the older age group, 61 years and above (odds ratio, 3.25 [1.32-8.03]; p = 0.011), and males were found to be at higher risk. Further research is needed to find the age and sex-related factors in determining vaccine effectiveness and adverse events.
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Vacunas contra la COVID-19 , COVID-19 , Vacunas , Adolescente , Adulto , COVID-19/epidemiología , COVID-19/etiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/uso terapéutico , ChAdOx1 nCoV-19/efectos adversos , ChAdOx1 nCoV-19/uso terapéutico , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2 , Vacunación/efectos adversos , Vacunas/efectos adversos , Vacunas/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVES: West syndrome is a severe epileptic encephalopathy of young age. It is characterized by a clinico-electrical triad of infantile epileptic spasms, regression or arrest of psychomotor development, and hypsarrhythmia. In the last two decades, the large progress in the development of newer antiepileptic drugs has allowed us to have a vast choice of treatment options to control spasms, although they often fail to do so. Thus, there is a need to explore other treatment options. MATERIALS & METHODS: Subjects in this open-labelled randomized control trial were included newly diagnosed children of age between 3 months and 5 years of both genders. A total of 52 children were recruited and randomized into two groups: an intervention group (n=30) and a non-intervention group (n=22). Magnesium sulphate was provided for the intervention group but not for the non-intervention one. Both groups received the rest of the treatments, including adrenocorticotropic hormone and antiepileptic drugs. The follow-up period was three months, at the end of which a per-protocol analysis was performed. RESULTS: There was no significant difference in seizure control and neurodevelopmental outcome between both groups, but electroencephalogram significantly improved in the intervention group compared to the control. Also, the clinical response was better in patients with normal initial serum magnesium levels in the intervention group (p=0.003) than in other patients. CONCLUSION: Magnesium supplementation may be helpful in children with West syndrome.
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With the advent of human civilization and anthropogenic activities in the shade of urbanization and global climate change, plants are exposed to a complex set of abiotic stresses. These stresses affect plants' growth, development, and yield and cause enormous crop losses worldwide. In this alarming scenario of global climate conditions, plants respond to such stresses through a highly balanced and finely tuned interaction between signaling molecules. The abiotic stresses initiate the quick release of reactive oxygen species (ROS) as toxic by-products of altered aerobic metabolism during different stress conditions at the cellular level. ROS includes both free oxygen radicals {superoxide (O2â¢-) and hydroxyl (OH-)} as well as non-radicals [hydrogen peroxide (H2O2) and singlet oxygen (1O2)]. ROS can be generated and scavenged in different cell organelles and cytoplasm depending on the type of stimulus. At high concentrations, ROS cause lipid peroxidation, DNA damage, protein oxidation, and necrosis, but at low to moderate concentrations, they play a crucial role as secondary messengers in intracellular signaling cascades. Because of their concentration-dependent dual role, a huge number of molecules tightly control the level of ROS in cells. The plants have evolved antioxidants and scavenging machinery equipped with different enzymes to maintain the equilibrium between the production and detoxification of ROS generated during stress. In this present article, we have focused on current insights on generation and scavenging of ROS during abiotic stresses. Moreover, the article will act as a knowledge base for new and pivotal studies on ROS generation and scavenging.
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Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estrés Fisiológico/fisiología , Animales , Cambio Climático , Daño del ADN/fisiología , Humanos , Peroxidación de Lípido/fisiología , Transducción de Señal/fisiologíaRESUMEN
PURPOSE: We identified calreticulin in human filaria Brugia malayi (BmCRT) that shares 97% homology with Wuchereria bancrofti calreticulin (WbCRT), but only 56% with human calreticulin. We found that BmCRT binds C1q and prevents complement-mediated parasite death; immunization with BmCRT leads to parasite death in a rodent model of the infection. BmCRT could, therefore, be a potential vaccine candidate. In the present study, we determined the levels of BmCRT-reactive IgG and its isotype in bancroftian filarial subjects. METHODS: Recombinant BmCRT (rBmCRT) was prepared, and the sera of endemic normal subjects (EN), microfilaraemics (Mf+) and chronic amicrofilaraemics (ChMf-) from a bancroftian filaria-endemic area and normal subjects from filaria-non-endemic area (NEN) were probed for IgG and its isotypes reacting with rBmCRT and its domains rN, rP and rC. RESULTS: rBmCRT and its rN domain-reactive IgG levels were high in EN and Mf+ groups; rC domain and rP domain showed moderate and very little reactivity, respectively. NEN sera were non-reactive. Moderate levels of rBmCRT-reactive IgG1, IgG3 and IgG4 in EN and Mf+ groups and low levels of IgG2 in Mf+ were found; IgG1 and IgG3 reactivity was found for rBmCRT and its rN domain only, while IgG4 reactivity was moderate for rN domain and low for rP and rC domains. While IgG reactivity was seen in all the endemic subjects, IgG isotype reactivity was found mostly in EN and Mf+ subjects. CONCLUSIONS: Moderate levels of rBmCRT (and its rN domain)-reactive IgG and its isotypes are present in bancroftian subjects. Preponderance of IgG1 and IgG3 isotypes which bind and activate complement has relevance to vaccine potential of BmCRT.
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Brugia Malayi , Filariasis Linfática , Vacunas , Animales , Anticuerpos Antihelmínticos , Antígenos Helmínticos , Calreticulina/metabolismo , Filariasis Linfática/prevención & control , Humanos , Inmunización , Inmunoglobulina GRESUMEN
Background: Several symptoms are typically experienced after a coronavirus disease 2019 (COVID-19) infection. Worldwide, a lot of women are reporting irregularities in their menstrual cycles post-COVID-19 infection. The purpose of this study is to investigate the prevalence of menstrual pattern among young girls during the second wave of COVID-19 pandemic and to determine the risk factors related to lifestyle among young girls. Methods: A cross-sectional study was conducted using a self-designed questionnaire encompassing details of the menstrual pattern, features of hyperandrogenism, lifestyle, and comorbidity among young girls aged 16-24 years. Results: The data from 508 girls fulfilling the inclusion criteria were analyzed. The prevalence of irregular menstrual cycle was found to be 29.1%. Further analysis revealed that a significant percentage of girls with irregular menstrual cycle suffer from depression (14.9%) and are often staying stressed (40.5%) in comparison to the girls having regular menstrual cycle. Also, a total of 58 girls out of 508 were diagnosed with polycystic ovary syndrome (PCOS). Among various comorbid conditions, obesity was found in 60% of girls having PCOS followed by an eating disorder. Conclusions: A significant increase in irregular menstrual cycle in young girls was found during the second wave of COVID-19. The risk factors for causing the irregular menstrual cycle were found to be insomnia, stress, and depression.
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Introduction: Agad Tantra being the unique branch that deals with toxicology and its management enlists several antitoxic drugs used for various poisonings. Ancient texts comprise the list of a wide range of traditional medicines, but they are not explored due to lack of incomprehension. Aims: The review has been written with the aim to dig out the hidden knowledge of Vishaghna Dravyas (alexeterics) mentioned in Kaiydeva Nighantu. Materials and methods: This Nighantu was written in the 15th century A. D. by Kaiydeva with the name "Pathya-Apathya-Vibodhaka" it comprising of total 514 Dravyas out of which 175 drugs possess Vishagna (anti-poisonous) property. Results: These Vishaghna Dravyas (alexeterics) have been distributed based on various Vargas (classes) which is described as 121 belonging to Ausghada Varga (drug class) as single drugs and four as groups, total of 16 from Dhatu Varga (metal class) as single drugs and one as compound or as a group, 9 from Dhanya Varga (cereal class) as a single drug, 15 in Dravya Varga as single drugs, and 5 as compound or as a group. Two each in Kritana Varga and Vihara Varga and one in Mansa Varga as compound or as a group. Out of all the 175 Vishagna Dravayas (alexeterics), 18 Dravyas (substances) are specific indications in combating particular types of envenomation or poisoning conditions. Conclusion: All the abovementioned drugs are screened for the purpose of revalidation to bring out their therapeutic utility.
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Aeromonas hydrophila, a Gram-negative bacterium, causes diseases in fish, resulting in excessive loss to the aquaculture industry. Aeromonas is a highly heterogeneous group of bacteria, and the heterogeneity of the genus is attributed to variation and diversity in the virulence factors and toxins among various Aeromonas strains. One of the major toxins aerolysin, secreted by the bacterium, causes hemorrhagic-septicemia and diarrhea and can serve as a drug target. Here, we describe characterization, molecular phylogeny, and homology modeling of the aerolysin of A. hydrophila strain EUS112 (AhEUS112) cloned in our lab. The encoded aerolysin is 485 amino acids long with an N-terminal signal sequence of 23 amino acids. Phylogenetic analysis of the aerolysin of AhEUS112 revealed that it belongs to a diverse group of toxins, showing maximum similarity with aerolysins of other Aeromonas strains followed by Vibrio toxin. The homology model of the mature aerolysin of AhEUS112 was generated using the crystal structure of a mutant aerolysin (PDB#3g4n) as the template, which showed that the encoded aerolysin exists as a channel protein. Validation of the generated model using bioinformatics tool confirmed it to be a good quality model that can be used for drug design. Molecular dock analysis revealed that drugs, aralia-saponin I, cyclamin, ardisiacrispin B, and aralia-saponin II bind to aerolysin with a higher affinity as compared to other drugs and at functionally important amino acids of aerolysin. Hence, these molecules can act as an effective therapeutics for inhibiting the aerolysin pore formation and curtail the severity of Aeromonas infection.Communicated by Ramaswamy H. Sarma.
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Aeromonas hydrophila , Aeromonas , Animales , Aeromonas hydrophila/genética , Aeromonas hydrophila/metabolismo , Filogenia , Aeromonas/genética , Aeromonas/metabolismo , Factores de Virulencia/metabolismo , Aminoácidos/metabolismoRESUMEN
Coronavirus disease-19 (COVID-19) pandemic is associated with high morbidity and mortality. COVID-19, which is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2), affects multiple organ systems through a myriad of mechanisms. Afflicted patients present with a vast constellation of symptoms, from asymptomatic disease to life-threatening complications. The most common manifestations pertain to mild pulmonary symptoms, which can progress to respiratory distress syndrome and venous thromboembolism. However, in patients with renal failure, life-threatening cardiac abnormalities can ensue. Various mechanisms such as viral entry through Angiotensin receptor (ACE) affecting multiple organs and thus releasing pro-inflammatory markers have been postulated. Nevertheless, the predictors of various presentations in the affected population remain elusive. An ameliorated understanding of the pathology and pathogenesis of the viral infection has led to the development of variable treatment options, with many more that are presently under trial. This review article discusses the pathogenesis of multiple organ involvement secondary to COVID-19 infection in infected patients.